Double Botulism

1
Double Botulism

• Kathleen Dollins, MD, MT(ASCP)
• Texas Tech University Health Sciences Center
• Department of Pediatrics
• Lubbock, Texas

2
Abstract

• Infant botulism is a rare but serious disease
  that can affect children up to 1 year of age, and
  it is the most common form of human botulism in
  the United States
• Infants typically present with constipation,
  weakness, and flaccid paralysis among other
  symptoms
• Prompt recognition of symptoms and early
  treatment can allow for a favorable outcome
• This case illustrates how clinical symptoms of
  botulism can vary and cause confusion in diagnosis

3
Background/Objectives

• This case
• Illustrates signs and symptoms that should be
  associated with infant botulism
• Provides an overview of infant botulism
• Demonstrates the importance of prompt
  administration of BabyBIG when infantile
  botulism is suspected

4
History of Present Illness

• CC Hypotonia decreased suck
• HPI Pt is a 6-week-old male who presented as a
  transfer from Midland secondary to hypotonia,
  decreased suck swallow, increased oral
  secretions on 8/18/08
• Pt was well until 8/15, when he became congested,
  fussy, and wouldnt feed
• Mom was concerned secondary to the decreased
  feeding and took the pt to 2 different ERs in
  Midland that evening. Infant was diagnosed with
  URI and sent home both times
• On 8/16, Mom again returned to Midland ER because
  her son had not taken any feedings the previous
  evening along with new onset floppiness
• Pt was then admitted for dehydration and
  hypotonia

5
HPI Continued

• On admission to a hospital in Midland, an LP was
  attempted but not successful. However, blood
  urine cultures were obtained
• Pt was started on Ampicillin Rocephin
• Pt did not improve during his 2 day stay was
  therefore transferred to UMC PICU in Lubbock
• Mom denied any history of fever, sick contacts,
  or trauma. The pt had not been given honey, corn
  syrup, canned food, or well water. There was no
  new construction near the home, however the
  neighbors were remodeling the inside of their home

6

• Birth History Full term, SVD. No complications
  with the pregnancy or delivery. BW 77oz.
  Normal newborn stay
• Past Medical History Negative
• Past Surgical History Negative
• Social Pt lives in Midland with his 21-year-old
  mother, maternal grandmother, maternal
  grandfather, 16-year-old aunt and 9-year-old
  uncle.
• The father is actively involved in the patients
  care.
• The family has 1 outside dog.
• There is no smoking in the home.
• There is no well water use.
• Patient was breastfed for 2 weeks, and has since
  fed with the premade liquid formula.
• There has been no recent travel.

7
Medical History Continued

• Family History Parents are healthy. No
  neurological disorders in the family. No history
  of CVA, hypertension, MI, or diabetes in the
  family.
• Developmental Pt was able to smile, track,
  lift his head up until 8/16. Since then, he has
  been unable to perform these milestones
• Immunizations UTD (1 Hepatitis B at birth)
• Allergies NKDA
• Meds Tylenol (80mg/0.8ml) 0.4ml x 1 on 8/15
  Ampicillin Rocephin while hospitalized in
  Midland

8
Review Of Systems

• General Positive for fussiness, Negative for
  fever
• HEENT Positive for congestion, rhinorrhea,
  oral secretions. Positive for decreased eye
  tracking movements. Negative for any eye
  redness, tearing or discharge.
• CV Negative for history of heart murmur
• Respiratory Positive for coughing noisy
  breathing
• GI Positive for decreased feeds. Negative for
  constipation, diarrhea, vomiting or spitting up.
  Last BM was 8/15 stools were normal until this
  point.

9
Review Of Systems Continued

• GU Negative for decreased urine output or foul
  smelling urine
• Musculoskeletal Positive for floppiness since
  8/16 with no improvement
• Skin Negative for any rashes
• Neurological Negative for any seizure like
  activity

10
Physical Exam

• Well nourished 6 week old Hispanic male with weak
  cry but no apparent distress on admission.
  Notable generalized hypotonia upon removal from
  car seat upon transfer to Lubbock
• Vitals Temp 98.2, Pulse 180, Resp 30, BP
  104/72, O2 96 on RA, Weight 5kg (50), Length
  57cm (50), FOC 41cm (90)
• HEENT AFSF, NC/AT, Pupils 4 to 2 sluggish.
  EOMI however pt would not make eye contact or
  track. TMs No erythema or bulging. Nose
  Clear/White rhinorrhea. OP High arched palate,
  mucous membranes moist without erythema or
  lesions. Lips noted to be very dry and OP had
  very thick clear secretions pooling in the
  posterior OP

11
Physical Exam

• Neck Supple, No LAD
• CV Good S1,S2. RRR. II/VI SEM at LLSB. CR lt
  2. Pulses 2 and symmetrical throughout
• Lungs Transmitted upper airway congestion but
  otherwise CTAB, no w/r/r. Slightly increased
  WOB, but no retractions noted.
• Abd Soft, NT, ND, Decreased BS, No HSM.
• GU Tanner I circumcised male, Testes descended
  bilaterally, No rashes noted
• Skin Warm Dry. No rashes noted. Band-aid
  present on spine from previous LP. Bruising 3
  puncture marks noted under bandage.

12
Physical Exam

• Ext Good muscle bulk, very decreased muscle
  tone throughout. No head control. Pt unable to
  keep his arm from dropping when elevated. Very
  decreased spontaneous movement of extremities
• Neuro No suck reflex, diminished gag.
  Questionable ptosis bilaterally. Sluggish
  pupils. No nystagmus. Reflexes 1 and
  symmetrical. Positive palmar plantar grasp.
  Babinski downgoing. Decreased response to pain.

13
Differential Diagnosis

• Infantile Botulism
• Meningoencephalitis
• Sepsis
• Myasthenia Gravis
• Werdnig Hoffman paralysis (SMA)
• Guillain-Barré syndrome

• Tick paralysis
• Metabolic derangements
• Hypocalcemia
• Hypernatremia
• Hypothyroidism
• Inborn errors of metabolism
• Myopathies
• Poliomyelitis
• Organophosphate poisoning
• Heavy metal poisoning

14
Labs obtained on admission to Lubbock

• CBCD
• WBC 8.5
• H/H 10.5/29.8
• Plt 560
• N18, L73, M7, TL 2
• BMP
• Na 137
• K 3.3
• Cl 105
• CO2 21
• BUN/Cr 2/0.2
• Gluc 125

• Ca 9.9
• TP 5.7
• Alb 3.6
• Tbili 0.4
• ALKP 259
• ALT 14
• AST 18
• CK 64
• Mg 1.7
• Lactic Acid 2.0

15
Labs Continued

• UA Neg nitrite, Neg LE, SG 1.021, Ph 6
• CSF
• RBC 2320
• WBC 115
• N8, L74, M18
• Gluc 84
• Prot 78
• Bld, Urine, CSF cx no growth (all hospitals)
• RDVP neg

• HSV PCR neg
• Acetylcholine receptor antibody negative
• CXR WNL
• CT MRI WNL
• EEG slowing
• EMG normal
• Stool for botulism toxin Clostridium botulinum
  type B and type F (2 months for confirmatory
  report)

16
Labs Continued

• Stool/Oropharynx for Enterovirus negative
• CSF for Enterovirus negative
• C.diff toxin - negative
• Cardiac Echo - WNL

17
Hospital Course

• LP done shortly after arrival to UMC PICU
• During LP, pt desaturated with bradycardia
• Procedure was stopped (no fluid obtained) and pt
  received BMV without complete recovery was then
  intubated and placed on a ventilator.
• LP re-attempted after pt stable on vent
• Ampicillin, Cefotaxime, and Acyclovir started at
  meningitic doses
• Neurology ID consulted both with suspicions
  of infantile botulism

18
Hospital Course Continued

• The following day, the pts neurological exam
  improved and EMG was normal. This decreased the
  suspicion for botulism, and BabyBIG was not
  ordered
• Opthalmology exam was WNL
• Pts neuro exam continued to improve, and pt
  began overbreathing the ventilator
• Attempted extubation 3 days after admission
  failed
• Ampicillin Cefotaxime stopped after 72 hours of
  negative cultures

19
Hospital Course Continued

• 5 days after admission, CT was repeated and was
  still WNL. EEG again showed slowing
• Hospital day 6
• Repeat LP
• Negative HSV PCR and Acyclovir was stopped
• Baby BIG ordered and given (45,000)
• Hospital day 7
• Normal repeat EMG
• Pt began PT OT for rehab
• Improved neuro exam (eye contact)
• Presumptive positive botulism stool culture from
  Tx Dept of Health (unknown type)

20
Hospital Course Continued

• Pt slowly continued to improve and was
  successfully extubated on hospital day 13 and
  discharged home on day 18
• Pt had a normal suck, swallow gag on discharge
• Clinic follow up 3 weeks after discharge
• Muscle tone greatly improved, but still notable
  head lag.
• 3 month f/u with Neurology
• Normal exam

21
Clostridium botulinum
22
Infantile Botulism

• Background
• Gram Positive, Spore forming anaerobe found in
  soil
• Classification
• 6 types Food-borne, wound, infantile, adult
  intestinal colonization, injection related,
  inhalational
• 7 toxin types (A-G) A, B, E,F are most common
  in humans

23
Infantile Botulism - Epidemiology

• Peak age 2-4 months
• Approximately 60 cases/year (with ½ in
  California)
• Most often acquired by swallowing microscopic
  dust particles that carry the spores
• Ingestion of honey occurs in less than 20 of
  cases

24
Outbreaks of infant botulism, by state, 1976-1996
25
Infantile Botulism

• Pathogenesis
• Occurs when swallowed spores colonize and produce
  botulinum exotoxin in the large intestine
• The exotoxin enters the blood and blocks
  acetylcholine release
• http//www.youtube.com/watch?vufQSPrLhJFwfeature
  related
• The incubation period varies from 3-30 days
• Morbidity Mortality
• Infant botulism progresses for 1-2 weeks and
  stabilizes for 2-3 weeks before recovery begins
• Average length of a hospital stay is 1 month
• Excretion of toxin may continue for more than 3
  months
• Case-fatality rate is 1.3

26
Infantile Botulism Physical Exam

• The degree of involvement can vary from
  asymptomatic to paralysis to sudden death
• The classic syndrome of botulism is a
  symmetrical, descending motor paralysis in an
  alert patient, with no sensory deficits
• Common sign is constipation
• Other clinical features include
• Listlessness
• Lethargy
• Difficulty in sucking and swallowing
• Hypotonia
• Weak cry
• Poor feeding
• Pooled oral secretions
• Generalized muscle weakness
• Poor head control

27
Infantile Botulism PE Continued

• Neurologic findings include
• Ptosis
• Ophthalmoplegia
• Sluggish pupil reaction to light
• Flaccid expression
• Dysphagia
• Weak gag reflex
• Poor anal sphincter tone
• Respiratory failure occurs in approximately 50
  of diagnosed patients
• Botulinum toxin does not cross the blood-brain
  barrier therefore sensation remains intact

28
Infantile Botulism DDx

• Sepsis
• Meningitis
• Spinal muscular atrophy
• Myasthenia gravis
• Tick paralysis
• Guillain-Barré syndrome
• Metabolic derangements
• Hypocalcemia
• Hypernatremia

• Hypothyroidism
• Inborn errors of metabolism
• Myopathies
• Poliomyelitis
• Organophosphate poisoning
• Heavy metal poisoning

29
Infantile Botulism Workup

• Stool and enema fluids are the specimens of
  choice
• Confirmation of toxin presence is via a mouse
  bioassay
• ID of the toxin type is performed by a mouse
  toxin neutralization test

30
Infantile Botulism Treatment

• Antitoxin Human derived Botulinum Immune
  Globulin (BabyBIG ) for A B toxins
• BabyBIG should be administered as soon as the
  clinical diagnosis is established
• Lab confirmation requires days
• Antitoxin does not reverse the muscle paralysis
  because it can only bind free neurotoxin in the
  blood
• Therefore it does prevent further progression of
  paralysis
• Average hospital stay for non-BabyBIG-treated
  patients is approximately 5.7 weeks.
• Patients treated with BabyBIG have an average
  stay of approximately 2.3 weeks
• ½ of all infants will require mechanical
  ventilatory support
• Enteral feedings should be started ASAP
• Aminoglycoside use should be avoided because they
  may increase the amount of free toxin in the
  large bowel

31
Infantile Botulism

• Follow Up
• The infant should have good to full recovery of
  muscle strength and tone before immunizations
  resume
• Live-virus vaccines (i.e., measles, mumps,
  rubella and varicella, Rotateq) will need to be
  delayed until 5 months after BabyBIG treatment
• Therefore, only patients who were 7 months of age
  or older when they were treated with BabyBIG
  will need delayed immunization with these
  vaccines
• C. botulinum can be excreted in the feces for up
  to 3 months after the infection
• Prognosis
• The prognosis for infant botulism patients is for
  full and complete recovery
• This results from regrowth of the nerve endings
• Botulinum toxin does not penetrate into the brain

32
References

• http//www.infantbotulism.org/
• Behrman R, Kliegman R, Jenson H. 2004. Nelson
  Textbook of Pediatrics 17th Edition.
  Philadelphia Elsevier Science. Pages 590-591
• Domingo RM, Haller JS, Gruenthal M. Infant
  botulism two recent cases and literature review.
  J Child Neurol. 2008 Nov23(11)1336-46
• Francisco AM, Arnon SS. Clinical mimics of infant
  botulism. Pediatrics. 2007 Apr119(4)826-8
• Nevas M, Lindström M, Virtanen A, Hielm S, Kuusi
  M, Arnon SS, Vuori E, Korkeala H. Infant botulism
  acquired from household dust presenting as sudden
  infant death syndrome. J Clin Microbiol. 2005
  Jan43(1)511-3.
• http//www.youtube.com/watch?vufQSPrLhJFwfeature
  related
• http//www.cdc.gov/ncidod/DBMD/diseaseinfo/files/b
  otulism_manual.htmIV