Case Studies: Public Health Laboratories Respond …...Analysis. Answers. Action. Case Studies: Public Health Laboratories Respond to Threats A Case of Four Wheeling Botulism in Minnesota

Analysis. Answers. Action. www.aphl.org

Case Studies: Public Health Laboratories Respond to Threats

A Case of Four Wheeling Botulism in Minnesota

Moe SullivanMinnesota Department of HealthPublic Health Laboratory Division

Infectious Disease Laboratory Section

Analysis. Answers. Action. www.aphl.orgCenter for Food Security and Public Health Iowa

Organism

• Clostridium botulinum– Gram positive– Obligate anaerobic bacillus– Spores

• Ubiquitous• Resistant to heat, light, drying and radiation

Presenter

Presentation Notes

Botulism is caused by the bacterium Clostridium botulinum. It is a gram positive, spore-forming, obligate anaerobic bacillus. The clostridial spores are ubiquitous in soil and are very resistant to heat, light, drying and radiation. Spores may survive boiling for several hours at 100 oC, however exposure to moist heat at 120 oC for 30 minutes will kill the spores. Specific conditions are required for the germination of spores. These include anaerobic conditions (such as rotting carcasses or canned food), warmth, and mild alkalinity. The photo shows the bacillus shape of the bacterium C. botulinum. (Source: CDC Public Health Image Library: http://phil.cdc.gov/Phil/detail.asp?id=2131).


Neurotoxins

• Seven different types: A through G– All cause flaccid paralysis – Only a few nanograms can cause illness– Different types affect different species

Presenter

Presentation Notes

After germination, clostridial spores release neurotoxins. There are 7 antigenic types of neurotoxins, classified as A through G. Typically, different neurotoxin types affect different species. Only a few nanograms of these toxins can cause severe illness. All cause flaccid paralysis in the species affected. Toxin is produced in improperly processed, canned, low-acid or alkaline foods, and in pasteurized and lightly cured foods held without refrigeration, especially in airtight packaging. The physiologic mechanism of the neurotoxin is to irreversibly bind at neuromuscular junctions to prevent the release of acetylcholine (Ach). This causes muscular paralysis. The peripheral sensory nerves and the central nervous system are usually not affected. The toxin can be destroyed heat and cooking food at 80oC for 30 minutes, however, inactivation of spores requires a much higher temperature.


Human Disease

• Three forms– Infants <1 (most common form in US)– Foodborne (most common from home-canned

foods)– Wound (spore enters wound in skin)

• All forms fatal and a medical emergency• Incubation period: 12-36 hours


Adult Clinical Signs

• Nausea, vomiting, diarrhea• Double vision• Difficulty speaking or swallowing• Descending weakness or paralysis

– Shoulders to arms to thighs to calves• Symmetrical flaccid paralysis• Respiratory muscle paralysis

Presenter

Presentation Notes

In humans, the clinical signs of botulism are similar for all forms of the disease. Gastrointestinal signs (i.e., nausea, vomiting, diarrhea) are usually the first signs to appear. They are followed acutely by neurological signs, such as bilateral cranial nerve deficits. The victim will have double vision, and difficulty seeing, speaking and swallowing. This soon develops into a descending weakness to symmetrical flaccid paralysis. This paralysis can affect the respiratory muscles and lead to death.


Infant Clinical Signs

• Constipation• Lethargy• Poor feeding• Weak cry• Bulbar palsies• Failure to thrive

Presenter

Presentation Notes

Children less than 1 year of age with the following clinical signs should be suspected of infant botulism. Constipation, lethargy, poor feeding, weak cry, bulbar palsies, failure to thrive, and progressive weakness. This can lead to impaired respiration and sometimes death if not treated promptly. The child in this picture is too weak to hold up its head as noted by the limp appearance of the neck and arms. It was an infant case of botulism. 72% of natural botulism cases occur in children under 1 year of age. California Department of Health Services http://www.dhs.cahwnet.gov/dcdc/InfantBot/toxfig2.htm


Botulism in Minnesota1999-2016• 15 cases infant botulism

– 10 toxin type B– 3 toxin type A

• 2 cases foodborne botulism (type A)

• 1 cases of wound botulism (type A)

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C. botulism in Minnesota

Toxin Type A Toxin Type B


Clostridium botulinum testing at MDH

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Clostridium botulinum tested at MDH

Toxin Type A Toxin Type B Toxin Type F

NOTE: Since 2013, all toxin A has been A silent B by PCR


LRN testing of botulism in Minnesota

• PCR– Toxin Type A, B, C, D, E, F and G

• ELISA (food and environmental only)– Toxin Type A, B, E and F

• Mouse Bioassay– Toxin Type A, B, and F

• Future: MALDI


LRN Testing

• Complicated– Not all labs can do MBA– Limited sample types– ELISA assay only good for two weeks– PCR testing

• Algorithm• Fussy!


Case A

• 12 YO Male• August 9 ATV accident

– Surgically repaired shoulder and scalp– Discharged August 11

• August 16– Difficulty swallowing– Weak and altered speech– Taken to ER –normal chest and head CT


Case A

• August 17– Transferred to Children’s in Minneapolis– “looked septic”– Pus in wound on shoulder– Intubated– Reactive left pupil, but right pupil was difficult

to assess because eye was swollen shut– Suspect ptosis in that eye


Case A

• Physician thinks of botulism, but defiantly not the classic presentation

• Patient did NOT have paralysis but did have progressive weakness

• Shoulder grew Enterobacter• 8/21 CDC consult on case and Anti-toxin

released


Summary of MDH testing of Case A

• Received 6 samples/isolates– Serum (low volume) only enough for MBA

• MBA inconclusive (one B mouse didn’t die)– Second Serum

• MBA positive for Toxin Type A – Isolated colony (called submitter to have them

send isolate to MDH)• PCR positive for Toxin Type A silent B• Confirmed as Toxin Type A by ELISA


Case B• 5 month old boy• 1/8/16 onset of mild, nondescript

symptoms• 1/12/16 seen at pediatrician for:

– Lethargy– Muted cry– Constipation– suspect URI- given supportive care and prune

juice


Case B• 1/15/16 seen by pediatrician for Well Child visit

– Hoarse cry– Mild congestion– CBC normal

• Pediatrician visit– Continued lethargy and constipation– Infant “seems floppier– Congestion and hoarse voice resolved– Referred to Neuro

• Neuro suspects botulism• Sends back to primary for stool culture


Summary of MDH testing of Case B

• MDH receives stool 2/13 – Toxin Type B detected by MBA, PCR and

ELISA• California does NOT release BabyBIG• 17th case of outpatient infant botulism

documented


Select Agent Reporting

• Form 4 for Identification– Toxin– Isolate

• Timing of reporting• Amended reports


Select Agent Documentation


Form 4 for Case A

• Complicated reporting


On a Side Note

• Francisella tularensis– 2015

• 4 animals• 4 humans

– 2016• 3 animals

• Brucella species– 2015

• 15 Brucella (4 MN residents and 7 from foreign clients)

– 2016• 3 Brucella (all from

foreign clients)

This means lots of Form 4’s for the Select Agent program


QUESTIONS?

Thank You!!!

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Case Studies: Public Health Laboratories Respond …...Analysis. Answers. Action. Case Studies: Public Health Laboratories Respond to Threats A Case of Four Wheeling Botulism in Minnesota