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Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose.
Now the Centers for Disease Control and Prevention (CDC) has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in Clinical Infectious Diseases early in 2018. The reviews addressed recognizing botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.
In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, ranitidine safe for infants attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, Maryland, told Medscape Medical News that the new guidance “was really specific (and) was meant to address the gap in guidance for mass casualty settings.”
While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a foodborne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.
Such a mass-casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, told Medscape Medical News that “botulism is rare and (so) could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.
Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, from wounds, and from inhalation, and iatrogenic botulism (from exposure via injection of the neurotoxin).
Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.
Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.
With foodborne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.
Edwards stressed to Medscape Medical News that, “Time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”
It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.
Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
Botulinum antitoxin is the only specific therapy for this infection. If given early — preferably within 24-48 hours of symptom onset — it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24-48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.
Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is < 2%, far lower than the mortality from untreated botulism.
While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that foodborne outbreaks and prevention issues are covered elsewhere on the CDC site.
Edwards has disclosed no relevant financial relationships. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.
Judy Stone, MD, is an infectious disease specialist and author of Resilience: One Family’s Story of Hope and Triumph Over Evil and of Conducting Clinical Research , the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.
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