botulism 1

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botulisbotulismm BY BY

Dr, WLAA SALAH MANAADr, WLAA SALAH MANAASPECIALEST OF PEDIATRIC SPECIALEST OF PEDIATRIC

مستشفى حميات كفر الشيخمستشفى حميات كفر الشيخ

Definition:Definition:• Is acute flaccid paralytic Is acute flaccid paralytic

illness caused by the illness caused by the neurotoxins produced neurotoxins produced by:by:

clostridium botioliniumclostridium botiolinium or or rarelyrarely neurotoxines of neurotoxines of c.butyricum & c.bratii.c.butyricum & c.bratii.

• It is Greek word (botulus)=sausage.It is Greek word (botulus)=sausage.

•where the Disease go its name from where the Disease go its name from out break in Germany in out break in Germany in 17931793 by by infected sausage.infected sausage.

TypesTypes::• 3 form of human botulism:3 form of human botulism: 1)infant botulism, (common in 1)infant botulism, (common in

USA)USA) 2)food borne botulism, (classic 2)food borne botulism, (classic

type)type) 3)wound botulism, (rare type).3)wound botulism, (rare type).

• Other non human typesOther non human types:: Avian botulism., Animal botulism.Avian botulism., Animal botulism.

EtiologyEtiology

Clostridium botulinum:Clostridium botulinum:It is : It is : gram +ve . gram +ve .

Spore forming. Spore forming.

Obligate anaerobe.Obligate anaerobe. need high pH. need high pH.

Its natural habitat:Its natural habitat: soil ,dust, marin sediment soil ,dust, marin sediment

Cbotulinum

In 1895, Emile Van Ermengem

first isolated the bacterium Clostridium botulinum

Toxins of botulism:Toxins of botulism:

• is !is ! Most poisonous substances known. Most poisonous substances known. (parental lethal dose is 10(parental lethal dose is 10--77 mg\kg. )mg\kg. ) (Just a teaspoon of pure botulism poison could kill millions (Just a teaspoon of pure botulism poison could kill millions

of people.)of people.) Action:Action: block neuromuscular junction transmission block neuromuscular junction transmission

Types:Types: A, B, C, D, E, F, G. A, B, C, D, E, F, G. C.butyricum C.butyricum E.E. C. baratii C. baratii FF..

• Spores Spores *Survive 2 hr at 100 °C.*Survive 2 hr at 100 °C. *Inactivated at 120 °C .*Inactivated at 120 °C . ( Boiling food before canning at high elevations may not ( Boiling food before canning at high elevations may not

inactivate the spores.)inactivate the spores.) *Factors favoring spore germination:*Factors favoring spore germination: Low acidity (pH > 6.0); Low O2; High water content .Low acidity (pH > 6.0); Low O2; High water content .• Toxins Toxins is heat labile=easily destroyed at 80 c or higher for 10 is heat labile=easily destroyed at 80 c or higher for 10

min. min. Inactivated after 1 minute at 85 °C, or 5 minutes at 80 °C.Inactivated after 1 minute at 85 °C, or 5 minutes at 80 °C.• Little is known about the ecology of C.butyricum &C. baratii.Little is known about the ecology of C.butyricum &C. baratii.

Toxins of botulism:Toxins of botulism:

• Effect :A B C E F Effect :A B C E F human botulism. human botulism. C D C D animal botulism. animal botulism. G G not known if human not known if human or animal.or animal.

ToxinsToxins is simple di_chain is simple di_chain

protein consisting of: protein consisting of:

*100 kd heavy bond *100 kd heavy bond neuronal neuronal attachmentattachment

*50 kd light bond *50 kd light bond

go inside !cell after go inside !cell after bindingbinding

EpidemiologEpidemiologyy

Infant botulismInfant botulism• Reported from all continents except Africa.Reported from all continents except Africa.

• Notably, the infant is the only ill member in the Notably, the infant is the only ill member in the Family.Family.

• Age: (3 w-6 m) (peak 2-4m) Age: (3 w-6 m) (peak 2-4m) (extreme 3day—382days).(extreme 3day—382days).

• Sex: equal.Sex: equal.

• It is uncommon to diagnose It is uncommon to diagnose (in USA 1,448)were reported from (in USA 1,448)were reported from 1976:1996)1976:1996)

Infant botulismInfant botulism• Risk factor: Risk factor: * ingestion of contaminated honey.* ingestion of contaminated honey. 10% of honey in USA may be contaminated with 10% of honey in USA may be contaminated with

spores. sospores. so not used bef. (6m-1yr) not used bef. (6m-1yr) * slow intestinal transit time (<1 stool / day).* slow intestinal transit time (<1 stool / day).

• Sources of sporesSources of spores ,home dust , vacuum ,home dust , vacuum cleaner dust, contaminated honey and may corn cleaner dust, contaminated honey and may corn syrup?. syrup?.

• Breast feedingBreast feeding protect against fulmination protect against fulmination and sudden death.and sudden death.

Food borne botulismFood borne botulism• Occur dt ingestion of food in which Occur dt ingestion of food in which C. botC. bot. .

had multiplied & produce its toxins.had multiplied & produce its toxins.

• In USA outbreak was occur either from In USA outbreak was occur either from canned food or other foodcanned food or other food

(e.g. sauté onion , baked potato, chopped (e.g. sauté onion , baked potato, chopped garlic, peyote tea, hazelnut flavoring added to garlic, peyote tea, hazelnut flavoring added to yogurt, sweet cream cheese, sauté onion in patty yogurt, sweet cream cheese, sauté onion in patty melt sandwiches)melt sandwiches)

Food borne botulismFood borne botulism• In USA in the Last 10 yrs 150 outbreak In USA in the Last 10 yrs 150 outbreak

from canned or uncooked food.from canned or uncooked food.

• Food with low acid (pH > 6.0) =Food with low acid (pH > 6.0) = home canned food as, home canned food as, jalapeno peppers, asparagus, olives, jalapeno peppers, asparagus, olives,

beansbeans..     ،والزيتون والهليون، جاالبينو، والزيتون، الفلفل والهليون، جاالبينو، الفلفلوالفاصولياوالفاصوليا

Food borne botulismFood borne botulism• Type A & B,,,,Type A & B,,,, produce strong produce strong

putrefactive odour. putrefactive odour.

• Type E ,,,,,,,,,,,Type E ,,,,,,,,,,, appeared in native appeared in native foods e.g. fermented salmon foods e.g. fermented salmon egg ,seal flippers that not produce egg ,seal flippers that not produce sign of spoilage .sign of spoilage .

another hazard of type E is another hazard of type E is abilities to grow below 5 c (refrig.) abilities to grow below 5 c (refrig.)

Wound botulismWound botulism

• Rare disease.Rare disease.• < 200 cases were reported WW .< 200 cases were reported WW .• Occur with traumatic injuries.Occur with traumatic injuries.• Occur even if no skin breakdown (crush inj.).Occur even if no skin breakdown (crush inj.).• In the last yrs from injection abusers In the last yrs from injection abusers

(heroin)(heroin) (even if no abscess). (even if no abscess).

PathogenesiPathogenesiss

PathogenesisPathogenesis• All 3 form of Disease have All 3 form of Disease have

the same paththe same path.. FoodFood Contaminated with Contaminated with

Clostridium sporesClostridium spores Clostridium Clostridium grows in Anaerobic conditions: grows in Anaerobic conditions: Produces Produces toxin toxin

Alkaline pH of intestine dissociates Alkaline pH of intestine dissociates toxin from associated proteins toxin from associated proteins

toxin is toxin is absorbed into into circulation circulation bl. Stream bl. Stream preph. preph.

Cholinergic synapses Cholinergic synapses Irreversible binding Irreversible binding

block Ach. Release block Ach. Release so impair :so impair : 1-neuromusc. transmission.1-neuromusc. transmission. 2-autonomic transmission.2-autonomic transmission.

Infant botulismInfant botulism• Ingestion of spores Ingestion of spores

spores germination & spores germination & multiplication multiplication production of toxins in production of toxins in the large intestine.the large intestine.

• ( So it is infection with ( So it is infection with spores)spores)

Food borne botulismFood borne botulism

• It is intoxication not infection .It is intoxication not infection .

(i.e. ingestion of toxins in uncooked or (i.e. ingestion of toxins in uncooked or improper preserved food. improper preserved food.

WoundWound botulismbotulism

• Spores germination and Spores germination and colonizationcolonization

Of traumatic tissue by Of traumatic tissue by C. butiliniumC. butilinium..

Pathology:Pathology:

• Toxins is not cytotoxinToxins is not cytotoxin so there is no so there is no microscopic or macroscopic pathology microscopic or macroscopic pathology (autopsy). (autopsy).

• Healing occurHealing occur by formation of new by formation of new motor end plat and re innervations.motor end plat and re innervations.

(which take about 4w in (which take about 4w in experimental animals) experimental animals)

Terminal axons at Neuromuscular junctions (Rat)

Botulinum toxin induces enlargement of NMJs (middle)& sprouting of nerve terminals (middle & top)

Clinical Clinical PicturePicture

Clinical Picture:Clinical Picture:• General role:General role: it is not possible to have it is not possible to have botulism with out having botulism with out having multiple bulbar palsies,, ,,,,,,,,,multiple bulbar palsies,, ,,,,,,,,,WHY?WHY?

As the Toxin is carried by ! Blood As the Toxin is carried by ! Blood & & because bulbar musculature havebecause bulbar musculature have

(relative high blood. Supply +high densities of (relative high blood. Supply +high densities of innervations. ).innervations. ).

So So all 3 form of !botulism all 3 form of !botulism symmetric symmetric descending flaccid paralysisdescending flaccid paralysis of Cr. Nerve of Cr. Nerve musculatures.musculatures.

Infant botulism:Infant botulism:• Very early cases & mild Very early cases & mild

cases may be missed.cases may be missed.

• Early: dec. N. of defecation Early: dec. N. of defecation constipation constipation or even or even loss of defecation.loss of defecation.

• Then : inabilities to feed – Then : inabilities to feed – week cry- dec. week cry- dec. spontaneous movement.spontaneous movement.

• Then Cr. Nerve palsiesThen Cr. Nerve palsies

Cr. Nerve palsiesCr. Nerve palsies• Dys phagia--------Dys phagia-------- drooling of mouth secretion. drooling of mouth secretion.• Diplopia.Diplopia.• Dry tongue.Dry tongue.• Dropped eye lid (ptosis).Dropped eye lid (ptosis).• Dysphonia.Dysphonia.• Dysarthria.Dysarthria.• Dec. gag & corneal reflexes. Dec. gag & corneal reflexes. • Dilated pupils.Dilated pupils.• Occulomotor palsy appear with frequent O/EOcculomotor palsy appear with frequent O/E (pup. Light reflex).(pup. Light reflex).

• Loss of head control .Loss of head control .

• Respiratory distress --Respiratory distress -- resp. arrest.resp. arrest.

(( Descending Descending pattern:pattern:

facial facial cervical cervical trunk trunk limb limb illius illius atonic bladder atonic bladder.).)

drymouth

slurred

double

breathing swallowingdrooping

blurry muscle

N.B. N.B. Fever :Fever : Only present in wound type or in food Only present in wound type or in food

born type except if complication.born type except if complication.

Par aesthesia Par aesthesia :: is not seen in botulism as toxins act is not seen in botulism as toxins act

only on motor nerves.only on motor nerves. only seen dt , anxiety & only seen dt , anxiety &

hyperventilation.hyperventilation.Sensorium:Sensorium: pt., remain conscious but its pt., remain conscious but its

evaluation is difficult dt., slurred evaluation is difficult dt., slurred speech.speech.

Food born botulism:Food born botulism:

• Start as GIT symptom: Start as GIT symptom: nausea ,vomiting ,diarrhea occur in nausea ,vomiting ,diarrhea occur in 1/31/3 of cases of cases (it is dt associated organism, metabolic (it is dt associated organism, metabolic byproduct of the growth of bacteria).byproduct of the growth of bacteria).

• Constipation occur once paralysis occur.Constipation occur once paralysis occur.

• Then Cr. Nerves palsies manifestations.Then Cr. Nerves palsies manifestations.

wound botulism.wound botulism.

• Clinical Picture,Clinical Picture, like food born like food born but milder. but milder.

Incubation Period:Incubation Period:food borne botulismfood borne botulism wound botulism.wound botulism.

( 18-36 hours )( 18-36 hours )Extremes ( 2 hr—8days Extremes ( 2 hr—8days ))

( 4—14days ( 4—14days ((

depending on how muchdepending on how muchpoison is in the foodpoison is in the food

Degree of botulism:Degree of botulism:

• Very mild form: minimal ptosis , minimal ptosis , flattened flaccid expression , flattened flaccid expression , minor dysphagia, dysphonia.minor dysphagia, dysphonia.

• Fulminant form : : rapid onset extensive paralysis .RD, rapid onset extensive paralysis .RD,

apnea.apnea.

DiagnosiDiagnosiss..

•Clinical pictureClinical picture is enough for diagnosis is enough for diagnosis acute onset of acute onset of

flaccid paralysis clear sensorium ,flaccid paralysis clear sensorium , no fever , no par aesthesiano fever , no par aesthesia..•Laboratory :Laboratory : * * CSF,CBC,CT, MRICSF,CBC,CT, MRI ,are normal sometime, ,are normal sometime, evidence of evidence of dehydration or starvation dehydration or starvation

ketosis.ketosis. * Plasma * Plasma nor epinephrinenor epinephrine : Reduced : Reduced

• Specific lab: (+ve in 46%)Specific lab: (+ve in 46%)

1) Presence of toxins in serum.1) Presence of toxins in serum.

2) Presence of toxins ± organism in 2) Presence of toxins ± organism in wound + stool.wound + stool.

3)Presence of toxins ± organism in food 3)Presence of toxins ± organism in food ( but large amount is needed)( but large amount is needed)

•EMG: EMG: * show defect in N.M. transmission.* show defect in N.M. transmission.• Food born & wound : Food born & wound : potentiation of ! Evoked m. actionpotentiation of ! Evoked m. action potential at higher frequency ofpotential at higher frequency of stimulation(50Hz).stimulation(50Hz).• Infant type : BSAP Infant type : BSAP (Brief, Small ,Abundant ,motor unit action Potential)(Brief, Small ,Abundant ,motor unit action Potential)

**Nerve conduction velocities & Nerve conduction velocities & sensory nerve functionsensory nerve function

are normal.are normal.

Differential DiagnosisDifferential Diagnosis

((2020))• Guillain-Barre syndrome (GBS) Guillain-Barre syndrome (GBS) • Myasthenia gravis .Myasthenia gravis .• Tick paralysis.Tick paralysis.• Stroke or CNS mass lesion. Stroke or CNS mass lesion. • Poliomyelitis.Poliomyelitis.• Encephalitis.Encephalitis.• Meningitis.Meningitis.• Organo phosphorus pois.Organo phosphorus pois.• Viral polyneuritis.Viral polyneuritis.• Aminoglycosids paralysis.Aminoglycosids paralysis.• Psycatric illness.Psycatric illness.• Metabolic coma (DM).Metabolic coma (DM).

•

Guillain-Guillain-BarreBarre

Guillain-Barre syndrome Guillain-Barre syndrome (GBS) particularly Miller (GBS) particularly Miller Fisher variant)Fisher variant) • ascending paralysis ascending paralysis • Miller Fisher variant may be descending Miller Fisher variant may be descending • Abnormal CSF protein 1-6 wk after Abnormal CSF protein 1-6 wk after

illness onset illness onset • Paresthesias commonly occur.Paresthesias commonly occur.• EMG shows abnormal nerve conduction EMG shows abnormal nerve conduction

velocity;velocity;• Outbreaks of GBS do not occur (unlike Outbreaks of GBS do not occur (unlike

botulism) botulism)

Myasthenia gravisMyasthenia gravis

• Dramatic improvement with edrophonium Dramatic improvement with edrophonium chloride (ie, chloride (ie, a positive Tensilon test),a positive Tensilon test),

• although some botulism patients may although some botulism patients may exhibit partial improvement following exhibit partial improvement following administration of edrophonium chloride administration of edrophonium chloride (ie, a (ie, a borderline Tensilon test)borderline Tensilon test)

• EMG shows EMG shows decrease in muscle action decrease in muscle action potentialspotentials with repetitive nerve stimulation with repetitive nerve stimulation

Aminoglycoside toxicityAminoglycoside toxicity

• ——History of History of recent exposurerecent exposure to to aminoglycoside antibioticsaminoglycoside antibiotics

——More likely to occur in the setting of More likely to occur in the setting of renal insufficiencyrenal insufficiency

——Most commonly seen with Most commonly seen with neomycinneomycin

PoliomyelitisPoliomyelitis

— —Febrile illness.Febrile illness.

— —CSF shows pleocytosis and increased CSF shows pleocytosis and increased protein.protein.

— —Altered mental status may be Altered mental status may be present.present.

— —Paralysis often asymmetric. Paralysis often asymmetric.

polioresp