Case-Patient 1

A 63-year-old woman was admitted to a hospital on November 22, 2006, after a 2-day history of abdominal pain, blurred vision, diarrhea, dysarthria, dysphagia, horizontal binocular diplopia, imbalance, and weakness in the arms and hands. No recent infections, wounds, or antimicrobial drug use were reported. After admission to the hospital, she experienced respiratory arrest, for which intubation and ventilation were required. The patient’s medical history included Crohn disease, bowel surgery, short bowel syndrome, hypertension, breast cancer, nephrolithiasis, and small fiber polyneuropathy (motor function was normal on nerve conduction studies 6 years earlier). A pathology report from 20 years earlier noted acute and chronic inflammation of the patient’s large and small bowels. No acute wounds or punctures were apparent on examination.

The neurologic examination showed a normal level of consciousness and mental state; reduced pupillary light responses; bilateral, symmetrical ophthalmoplegia; bilateral ptosis; bifacial lower motor neuron weakness; moderate proximal and distal symmetrical limb weakness; absent tendon reflexes; and flexor plantar responses. Muscle tone was decreased; neither atrophy nor fasciculation occurred, and sensation was intact. Results of routine blood and urine tests showed only a mild elevation of the serum amylase level. Botulism was strongly suspected. However, other conditions that affect the central nervous system, including the brainstem and cranial nerves, were considered. Results of tests for syphilis, Lyme disease, West Nile virus infection, acetylcholine receptor antibodies, and IgG against GQ1b were negative.

Results of cerebrospinal fluid studies, including cytology and viral PCR studies, were also normal. A magnetic resonance imaging scan of the brain had unremarkable findings. Electrodiagnostic studies showed mildly reduced compound motor action potential amplitudes and normal sensory responses. Posttetanic facilitation was marked, with a 700% increase in compound motor action potential amplitudes. Electromyography showed that lower limb muscles were electrically silent. Enema fluid, stool, and gastric aspirate specimens were positive for type A botulinum neurotoxin and viable C. botulinum type A spores, with organisms persisting in stool for 61 days. Botulinum antitoxin was administered in the evening of November 23, 2006.

The environmental investigation found that the patient ate a limited diet of tea, bagels, peanut butter, occasional honey, and weekly Chinese take-out food. An opened jar of peanut butter from the patient’s residence yielded positive test results for C. botulinum type A spores, containing ≈14 C. botulinum spores/kg.

Figure

Figure. Results of pulsed-field gel electrophoresis of samples from case-patient 1, who had intestinal toxemia botulism, Ontario, Canada, 2006–2008. Lanes 1, 3: Clostridium botulinum type A isolated from enema sample; lanes 2,...

Both heated and nonheated samples from the enema fluid were positive for C. botulinum type A, indicating the presence of spores. Analysis of clinical and peanut butter isolates by PFGE indicated identical PFGE patterns (Figure).

The patient was still mechanically ventilated as of December 15, 2006, and required regular sedation. Once sedation wore off, the patient experienced random, spastic-like, nonpurposeful movements of all extremities. Her condition improved over the next 6 months, and she could walk by the time she was discharged.

Case-Patient 2

Bulbar symptoms developed in a 50-year-old woman with ophthalmoparesis on February 7, 2007, and her symptoms worsened until she was admitted to the hospital on February 10, 2007, with complete ophthalmoplegia, dysphagia, and quadriparesis. The patient’s medical history included a diagnosis of Crohn disease in 1979 and 4 previous bowel resections with ileocolonic anastomosis, complicated by enterocutaneous fistulas (in 1986, 1995, 2001, and 2002). She had no wounds, and no chest or abdominal pains were reported before the onset of symptoms. The patient experienced oropharyngeal discomfort and difficulty speaking but was able to respond to questions with a yes or no. A repeat computed tomography scan was carried out, and results were normal. Lumbar puncture was conducted for full studies, including tests for West Nile virus. Over the next 24 hours, she had a decreased level of consciousness, a depressed Glasgow coma scale score, tachycardia, and difficulty breathing, with eventual respiratory failure requiring ventilation support.

The neurologic examination showed minimal orbicularis oculi contractions and quadriparesis with normal reflexes. The differential diagnoses being considered for this case-patient included the following: viral encephalitis, meningitis, brain stem lesion, myasthenia gravis, and infectious agents, specifically, C. botulinum and enteric organisms linked to Guillain-Barré syndrome, such as Campylobacter, Salmonella, and Shigella spp. The initial assessment by the consulting neurology team was that of Miller Fischer variant of Guillain-Barré syndrome and Eaton-Lambert syndrome or acute motor axonal neuropathy. Electromyography studies showed myopathic-like motor unit action potential. Results of a Tensilon test were negative. Additional tests, including a test for antibody against acetylcholine, and repeat electromyography studies with high frequency stimulation were negative (no incremental response and a negative acetylcholine antibody test results), which indicated that myasthenia gravis and Eaton-Lambert syndrome were unlikely. A presumptive diagnosis of botulism from intestinal toxemia, based in part on the patient’s history of Crohn disease and previous bowel surgeries, was made on February 13, 2007. The patient received botulinum antitoxin on February 23, 2007. She remained dependent on a ventilator for 5 months and had a percutaneous endoscopic gastrostomy tube for feeding, leading to line sepsis on 2 occasions, ventilator-assisted pneumonia, and a tracheostomy.

The patient’s food history included consumption of toast with peanut butter, coffee, chicken soup, and home-prepared beef tacos with grated cheese, lettuce, tomatoes, and salsa. Before the onset of symptoms, the patient consumed peanut butter daily. An opened jar of peanut butter from the home yielded positive test results for C. botulinum type A.

Of 7 serum samples, the first sample was positive for botulinum neurotoxin; however, the quantity was insufficient for serotype determination. Subsequent serum sample test results were negative for botulinum neurotoxin. Type A botulinum toxin was detected in the first stool specimen, which was collected on February 21, 2007. All subsequent stool specimen test results were negative for botulinum toxin. Test results for 5 of 8 stool specimens were positive for either C. botulinum type A or type B spores over 56 days. Three subsequent stool samples collected in May 2007 yielded negative test results for C. botulinum.

The patient was transferred to a rehabilitation hospital on June 17, 2007, where she required nightly ventilation support and received therapy for swallowing and speech as well as physiotherapy and occupational therapy. In September 2007, ventilator support was gradually withdrawn; the patient learned to eat on her own and was discharged, but she continued to receive outpatient therapy for an additional 3 months. During a follow-up visit in June 2009, the patient was walking independently, and a respiratory evaluation showed normal ventilatory capacity of forced expiratory volume of 2.58 L, 99% of predicted normal inspiratory muscle strength, and only minimal expiratory muscle weakness.

Case-Patient 3

A 45-year-old man with no known history of gastrointestinal problems and otherwise healthy was admitted to the hospital on January 8, 2008, with a distended abdomen and blurry vision (15). The patient’s abdomen continued to distend, and bowel sounds were diminished despite nasogastric suctioning. No recent infections or antimicrobial drug therapy were noted. The distended abdomen signaled a possible bowel obstruction, and scans confirmed the presence of an obstruction with unknown cause. A neurologic consultation was necessary after 5 days to assess the patient’s worsening neurologic symptoms. Guillain-Barré syndrome and myasthenia gravis were initially considered, but results of a nerve conduction study were classic for botulism. Botulism was suspected on January 14, 2008, on the basis of neurophysiologic findings, coupled with the clinical observations suggestive of botulism.

Clinical samples were subsequently sent for analysis, and through consultation with the physician, neurologist, and public health practitioners, it was determined that the patient would still benefit from antitoxin, even though it had been more than 24 hours since the onset of symptoms. Antitoxin was administered the evening of January 14, 2008. The patient remained hospitalized until February 27, 2008, when clinical symptoms improved. C. botulinum type B was detected in the patient’s stool at weeks 2 and 8 after the onset of symptoms. Botulinum neurotoxin was not detected in the stool extracts. Resulting of testing of both heated samples were positive for C. botulinum type B, indicating the presence of spores in the sample. Two subsequent fecal samples at weeks 11 and 15 yielded negative test results for C. botulinum. The persistence of C. botulinum type B over a period of 41 days supported the diagnosis of intestinal toxemia botulism. The patient had a history of eating primarily commercial canned food, although no specific types were reported, and none of the patient’s contacts were reported to be ill.