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The mouse bioassay is the standard test for botulinum neurotoxin. MALDI-TOF mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight) can be 10 to 100 times more sensitive, but is not yet widely available. The Los Angeles County Department of Public Health runs the bioassay itself and routinely sends botulism specimens to CDC for mass spectrometry too. In November 2017, that caught two cases the bioassay missed.
Case 1: botulism from the gut
An elderly man with no serious health problems was admitted in mid-November after 3 days of slurred speech, trouble swallowing and shortness of breath.
| Day after symptoms began | |
|---|---|
| 4 | put on a breathing machine for respiratory failure; then drooping eyelids, eye-movement paralysis and weakness in all four limbs |
| 16 | the health department is consulted about botulism and releases heptavalent botulinum antitoxin (HBAT) — but doctors hold it, suspecting myasthenia gravis; blood is drawn |
| 24 | the blood tests negative by mouse bioassay |
| 35 | mass spectrometry of the same blood confirms botulinum toxin type A; antitoxin is again held |
| 48 | stool is collected |
| 68 | the stool tests positive for type A toxin by mouse bioassay |
| 69 | antitoxin given — with no change |
| 109 | he dies of ventilator-associated pneumonia |
No risky foods, sick contacts or usual risk factors (such as bowel abnormalities or recent antibiotics) were found. The toxin-producing Clostridium botulinum kept being shed for a long time, which fits adult intestinal colonization botulism — only one or two cases a year in the United States.
Case 2: after botulinum toxin injections
In late November, a middle-aged woman came to an emergency department with trouble swallowing and a hoarse voice, but no breathing trouble or weakness. Five days earlier she had had botulinum toxin A injections, at FDA-approved doses and guided by electromyography, for cervical dystonia (neck muscle spasms). The health department released antitoxin, she received it, and she went home improved the next day.
Her blood, drawn before treatment, was negative by mouse bioassay (reported on day 5) but positive for type A toxin by mass spectrometry (day 41). The clinic reported the adverse event to the FDA's MedWatch; an inspection found no problems with its injection practices or doses. Her symptoms are local effects expected after these injections, and it is unknown whether they would have spread without antitoxin.
Lessons
- Mass spectrometry is more sensitive than the mouse bioassay, which matters for surveillance.
- But specimens must go to CDC, and results can take 2–4 weeks. Because paralysis can come on fast, antitoxin should usually be given on clinical grounds for suspected botulism, without waiting for tests, to stop progression or respiratory failure.
- Clinicians must report suspected botulism immediately to local and state health officials, who are available around the clock for advice, antitoxin, exposure investigation and testing guidance.
- For someone with only local symptoms after botulinum toxin injections, clinicians and health officials might monitor the patient and give antitoxin if signs of spreading weakness appear.
Sources
Based on "Notes from the Field: Intestinal Colonization and Possible Iatrogenic Botulism in Mouse Bioassay–Negative Serum Specimens — Los Angeles County, California, November 2017," by Umme-Aiman Halai and others, MMWR Morbidity and Mortality Weekly Report, volume 67, Centers for Disease Control and Prevention; a work of the United States government in the public domain.
Лицензия: CC0 1.0 (общественное достояние) · По материалам www.cdc.gov
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