Presentation is loading. Please wait.

Presentation is loading. Please wait.

بسم الله الرحمن الرحيم BIODEFENSE Epidemiology of Botulism Shahid Beheshti University of medical sciences, April 2005 By: Vahdani P. MD. MPH, Hatami H.

Similar presentations


Presentation on theme: "بسم الله الرحمن الرحيم BIODEFENSE Epidemiology of Botulism Shahid Beheshti University of medical sciences, April 2005 By: Vahdani P. MD. MPH, Hatami H."— Presentation transcript:

1 بسم الله الرحمن الرحيم BIODEFENSE Epidemiology of Botulism Shahid Beheshti University of medical sciences, April 2005 By: Vahdani P. MD. MPH, Hatami H. MD. MPH

2 2 Definition Disease – botulismDisease – botulism Agent – botulinum toxinAgent – botulinum toxin Source of toxin - Clostridium botulinumSource of toxin - Clostridium botulinum بوتوليسم نوعي بيماري عفوني همراه با فلج شل پايين رونده است كه در اثر توكسين بوتولينــوم ( Botulinum ) توليد شده بوسيله گونه هـــاي كلوستريديوم بوتولينوم، ايجاد مي شود بوتوليسم نوعي بيماري عفوني همراه با فلج شل پايين رونده است كه در اثر توكسين بوتولينــوم ( Botulinum ) توليد شده بوسيله گونه هـــاي كلوستريديوم بوتولينوم، ايجاد مي شود

3 3 History Therapeutic use of botulinum toxinTherapeutic use of botulinum toxin –FDA approved for neuromuscular disorders BlepharospasmBlepharospasm StrabismusStrabismus TorticollisTorticollis –Many other unapproved uses –Packaged in dilute preparations Not feasible to use licensed toxin for weaponNot feasible to use licensed toxin for weapon

4 4 Therapeutic Uses of Botulism Toxin Focal dystonias - involuntary, sustained, or spasmodic patterned muscle activityFocal dystonias - involuntary, sustained, or spasmodic patterned muscle activity Spasticity - velocity-dependent increase in muscle toneSpasticity - velocity-dependent increase in muscle tone Nondystonic disorders of involuntary muscle activityNondystonic disorders of involuntary muscle activity Strabismus (disorder of conjugate eye movement) and nystagmusStrabismus (disorder of conjugate eye movement) and nystagmus Disorders of localized muscle spasms and painDisorders of localized muscle spasms and pain Smooth muscle hyperactive disordersSmooth muscle hyperactive disorders Cosmetic useCosmetic use Sweating disordersSweating disorders

5 5 Bioweapon Potential Known unsuccessful uses as weaponKnown unsuccessful uses as weapon – aerosol releases by Aum Shinrikyo Downtown Tokyo, JapanDowntown Tokyo, Japan 3 times at US Military bases in Japan3 times at US Military bases in Japan Weapons ProgramsWeapons Programs –1930s Japanese fed C. botulinum to prisoners –U.S. produced botulinum toxin during WWII –Soviet Union spliced genome into other bacteria –1991 Iraq weaponized 19,000L during Persian Gulf War

6 6 Bioweapon Potential Botulinum toxin a major threat because:Botulinum toxin a major threat because: –Extreme potency and lethality –Ease of production –Ease of transport –Need for prolonged intensive care Top 6 potential biological warfare agentsTop 6 potential biological warfare agents Listed as Category A agent: High priorityListed as Category A agent: High priority

7 7 Critical Biological Agents Category A Variola majorVariola major Bacillus anthracisBacillus anthracis Yersinia pestisYersinia pestis Clostridium botulinumClostridium botulinum Francisella tularensisFrancisella tularensis Ebola hemorrhagic feverEbola hemorrhagic fever Marburg hemorrhagic feverMarburg hemorrhagic fever Lassa & JuninLassa & Junin

8 8 Bioweapon Potential Factors suggesting intentional releaseFactors suggesting intentional release –Large # cases Acute flaccid paralysis with bulbar palsiesAcute flaccid paralysis with bulbar palsies –Unusual botulinum toxin type Type C, D, F, or GType C, D, F, or G Type E not acquired from aquatic foodType E not acquired from aquatic food –Common geographic factor among cases No common dietary exposure - Suggests aerosolNo common dietary exposure - Suggests aerosol –Multiple simultaneous outbreaks without common source

9 9 Bioweapon Potential Estimated EffectEstimated Effect Most toxic substance knownMost toxic substance known –1 gram crystalline toxin can kill > 1 million people if dispersed and inhaled evenly –Point source aerosol release Incapacitate/kill 10% of people downwind within 500 metersIncapacitate/kill 10% of people downwind within 500 meters

10 10 Bioweapon Potential Naturally occurring botulismNaturally occurring botulism 1.Foodborne (preserved or non- preserved) 2.Wound 3.Intestinal Bioterrorism routes of intoxicationBioterrorism routes of intoxication –Aerosol (inhaled into lungs) –Foodborne –Waterborne ???

11 11 Bioweapon Potential Inhalational exposureInhalational exposure –One documented accidental outbreak Germany 1962Germany laboratory workers3 laboratory workers Exposed to re-aerosolized toxin type AExposed to re-aerosolized toxin type A Confirms that aerosol route is effective means of intoxicationConfirms that aerosol route is effective means of intoxication

12 12 Bioweapon Potential Food-borne botulismFood-borne botulism –Foods that are higher pH corn, pepper, carrots, beans,corn, pepper, carrots, beans, –Contaminated condiments –Commercial foods Difficult to distinguish intentionalDifficult to distinguish intentional

13 13 Bioweapon Potential Water-borne botulismWater-borne botulism No instances of water-borne botulism have ever been reportedNo instances of water-borne botulism have ever been reported Contamination of water supply is possibleContamination of water supply is possible Toxin would be rapidly inactivated by the chlorine used to purify drinking waterToxin would be rapidly inactivated by the chlorine used to purify drinking water Harrison 2005 pp. 1286

14 14 Municipal water plants unlikely sourceMunicipal water plants unlikely source –Botulinum toxin inactivated by standard potable water treatments (chlorination, aeration) –Slow turnover time of large-capacity reservoirs However, in untreated water or beverages the toxin may be stable for several daysHowever, in untreated water or beverages the toxin may be stable for several days Bioweapon Potential

15 15 Epidemiology U.S. incidenceU.S. incidence –< 200 annual cases of all forms –Approx 9 annual outbreaks of food- borne median of 24 casesmedian of 24 cases Recent trend toward restaurant rather than home-preserved foodsRecent trend toward restaurant rather than home-preserved foods All ages and genders equally susceptibleAll ages and genders equally susceptible MortalityMortality –25% prior to 1960 –6% during 1990’s

16 16 Epidemiology وضعيت بيماري در ايران و مطالعات انجام شده مطالعات ده ساله در انستيتو پاستور؟ سروتايپ ‌ هاي مختلف در ايران؟ آلودگي مواد غذائي مختلف در ايران؟ مطالعات انجام شده در بيمارستان لقمان حكيم تهران؟ مسموميت در قزوين؟ مسموميت در چابهار؟

17 17 كتاب بوتوليسم و مسموميت غذائي، دكتر پرويز وحداني

18 18 كتاب بوتوليسم و مسموميت غذائي، دكتر پرويز وحداني

19 19 Epidemiology Incubation periodIncubation period –Depends on inoculated dose –Inhalational hours in primate studies12-18 hours in primate studies 72 hours in 3 known inhalational cases72 hours in 3 known inhalational cases True incubation period is unknownTrue incubation period is unknown –Foodborne 6 hours to 8 days6 hours to 8 days –Wound 7.5 days (range 4-18 days) after injury7.5 days (range 4-18 days) after injury

20 20 Microbiology C. BotulinumC. Botulinum –Gram-positive obligate anaerobic bacillus –Spore-forming –Produces botulinum toxin –Heat sensitive as bacillus –Prefers low acid environment

21 21 Microbiology C. Botulinum sporesC. Botulinum spores –Ubiquitous SoilSoil Airborne dustAirborne dust Surfaces of raw fruits and vegetablesSurfaces of raw fruits and vegetables SeafoodSeafood –Heat resistant, hardy

22 22 Microbiology Botulinum toxinsBotulinum toxins –Consist of light and heavy chains Light chain – zinc endopeptidaseLight chain – zinc endopeptidase –The bioactive component –Colorless, odorless –Environmental survival Inactivated by heat >85ºC for 5 minInactivated by heat >85ºC for 5 min pH <4.5pH <4.5

23 23 Microbiology Toxin ClassificationToxin Classification –All have same clinical effect –Types A-G, antigenically distinct Type A- 54%, Type B- 15%, Type E- 27%Type A- 54%, Type B- 15%, Type E- 27% Type A- Western U.S., Type B- EasternType A- Western U.S., Type B- Eastern Types C, D reported in animals onlyTypes C, D reported in animals only Type G in soil samples onlyType G in soil samples only Humans likely susceptible to all typesHumans likely susceptible to all types

24 24 Pathogenesis Possible routes of exposurePossible routes of exposure –Inhalation of toxin (in a biological attack) –Food or water toxin contamination –Wound infected with C. Botulinum –Ingestion of C. botulinum

25 25 Botulism Toxin Mechanism

26 26 Pathogenesis Estimated lethal human doseEstimated lethal human dose Crystalline type A toxinCrystalline type A toxin  g given iv or im  g given iv or im  g inhalationally  g inhalationally 70  g given po70  g given po

27 27 Pathogenesis Toxin must enter bodyToxin must enter body –Direct toxin absorption from mucosal surface Gut – foodborneGut – foodborne Lungs – inhalationalLungs – inhalational –Via toxin produced by infection with C.botulinum Skin breaks – wound botulism after trauma, IV drugsSkin breaks – wound botulism after trauma, IV drugs Gut – intestinal botulismGut – intestinal botulism Would not be seen in BT event, as toxin would be usedWould not be seen in BT event, as toxin would be used Does not penetrate intact skinDoes not penetrate intact skin

28 28 Pathogenesis All forms of disease lead to same processAll forms of disease lead to same process –Toxin absorbed into bloodstream –Irreversibly binds peripheral cholinergic synapses –Cleaves fusion proteins used by neuronal vesicles to release acetylcholine into neuromuscular junction –Blocks Acetylcholine release permanently Results in paralysis of that muscleResults in paralysis of that muscle –Reinnervation via regeneration of axon twigs Takes weeks to monthsTakes weeks to months

29 29 Clinical Features Symptoms All forms same neuro symptomsAll forms same neuro symptoms –Diplopia / blurred vision –Ptosis –Slurred speech –Dysphagia / dry mouth –Muscle weakness

30 30 Infant Botulism Most common form in U.S.Most common form in U.S. Spore ingestionSpore ingestion –Germinate then toxin released and colonize large intestine Infants < 1 year oldInfants < 1 year old – 94% < 6 months old Spores from varied sourcesSpores from varied sources –Honey, food, dust, corn syrup

31 31 Infant Clinical Signs ConstipationConstipation LethargyLethargy Poor feedingPoor feeding Weak cryWeak cry Bulbar palsiesBulbar palsies Failure to thriveFailure to thrive

32 32 Clinical Features Classic TriadClassic Triad –Symmetric, descending flaccid paralysis with prominent bulbar palsies –Afebrile –Clear sensorium Bulbar palsies summarized as "4 Ds"Bulbar palsies summarized as "4 Ds" –Diplopia, dysarthria, dysphonia, dysphagia

33 33 Clinical Features Requested to perform max. smile. Ptosis, disconjugate gaze, mild asymmetric smile. Patient at rest, bilateral mild ptosis, disconjugate gaze, symmetric facial muscles.

34 34 Clinical Features Symptom progressionSymptom progression –Descending paralysis Lose head controlLose head control Lose gag – require intubationLose gag – require intubation Lose diaphragm – mechanical ventilationLose diaphragm – mechanical ventilation –Loss of deep tendon reflexes

35 35 Clinical Features Gastrointestinal/UrinaryNeurologicMuscular Nausea Dry Mouth Symmetrical skeletal Muscle weakness Vomiting Blurry vision Respiratory muscle paralysis DiarrheaDiplopiaFatigue Abdominal Pain Dilated or unreactive pupils Dyspnea Intestinal ileus Dysphagia Urinary retention Decreased gag reflex

36 36 Clinical Features 4 clinical forms of botulism4 clinical forms of botulism 1)Food-borne (first described in 1897) 2)Wound (1943) 3)Infant (1976) 4)Indeterminate (1977)

37 37 Clinical Features InfantInfant –Occurs in children < one year old –Ingests spores, grows in bowel & release toxin –Intestinal colonization of organisms –Normal intestinal flora not developed

38 38 Clinical Features IndeterminateIndeterminate –No specific food or wound source identified –Similar to infant but occurs only in adults –Risk factor: surgical alterations of the GI tract and/or antibiotic therapy –Leads to colonization

39 39 Diagnosis Clinical diagnosisClinical diagnosis Diagnostic tests help confirmDiagnostic tests help confirm –Toxin neutralization mouse bioassay Serum, stool, or suspect foodsSerum, stool, or suspect foods –Infant botulism C botulinum organism or toxin in fecesC botulinum organism or toxin in feces

40 40 Diagnosis What to do at first suspicion of a caseWhat to do at first suspicion of a case –Immediately notify public health dept –Acquire therapeutic antitoxin –Send samples for diagnostic testing Serum, vomit, gastric aspirate, suspect food, stoolSerum, vomit, gastric aspirate, suspect food, stool Collect serum before antitoxin givenCollect serum before antitoxin given If enema required, use sterile waterIf enema required, use sterile water Refrigerate samples and suspect foodsRefrigerate samples and suspect foods Get medication list to rule out anticholinesterasesGet medication list to rule out anticholinesterases

41 41 Diagnosis ConfirmationConfirmation –Takes 1-4 days –Available only at CDC and state public health labs Mouse BioassayMouse Bioassay –Type-specific antitoxin protects vs. toxin in sample –The assay can detect at minimal 0.03ng of toxin. CultureCulture –Fecal and gastric specimens cultured anaerobically –Results in 7 to 10 days

42 42 Diagnosis Differential diagnosisDifferential diagnosis –Guillain-Barre, myasthenia gravis Unique features to help in diagnosisUnique features to help in diagnosis –Disproportionate cranial nerve palsies –More hypoxia in facial muscles than below neck –Lack of sensory changes The diagnosis is suspected on clinical grounds and confirmed by a mouse bioassay or toxin immunoassay. HA 2005

43 43 Botulism Differential Diagnoses Guillain-Barré syndromeGuillain-Barré syndrome Myasthenia gravisMyasthenia gravis StrokeStroke Tick paralysisTick paralysis Lambert-Eaton syndromeLambert-Eaton syndrome Psychiatric illnessPsychiatric illness PoliomyelitisPoliomyelitis Diabetic ComplicationsDiabetic Complications Drug intoxicationDrug intoxication CNS infectionCNS infection OverexertionOverexertion

44 44

45 45 كتاب بيوتروريسم، دكتر حسين حاتمي

46 46 Treatment Supportive careSupportive care –Enteral tube feeding or parenteral nutrition –Mechanical ventilation –Treatment of secondary infections Avoid aminoglycosides and clindamycinAvoid aminoglycosides and clindamycin –Worsens neuromuscular blockade

47 47 ترندلنبرگ معكوس Do not give aminoglycosides and clindamycin

48 48 Treatment Passive immunization - equine antitoxin ( IU)Passive immunization - equine antitoxin ( IU) –Antibodies to Types A, B and E toxins –Binds and inactivates circulating toxin –Stops further damage but doesn’t reverse –Administer ASAP for best outcome –Dose per package insert Heptavalent antitoxinHeptavalent antitoxin –Investigational –Effective against all toxins

49 49 Treatment Antitoxin actionAntitoxin action –Food-borne botulism Neutralizing antibody levels exceed toxin levelsNeutralizing antibody levels exceed toxin levels Single dose adequateSingle dose adequate –Large exposure (e.g. biological weapon) can confirm adequacy of neutralizationcan confirm adequacy of neutralization – recheck toxin levels after treatment Antitoxin adverse effectsAntitoxin adverse effects –Serum sickness (2-9%), anaphylaxis (2%)

50 50 Treatment Recovery takes weeksRecovery takes weeks –Until motor axon twigs regenerate Special groups - same treatment strategySpecial groups - same treatment strategy –Children –Pregnant women –Immunocompromised

51 51 Levels of Prevention Primary Prevention:Primary Prevention: Prevention of disease in “well” individuals Prevention of disease in “well” individuals Secondary Prevention:Secondary Prevention: Identification and intervention in early stages of disease Identification and intervention in early stages of disease Tertiary Prevention: Tertiary Prevention: Prevention of further deterioration, reduction in complications Prevention of further deterioration, reduction in complications

52 52 Post Exposure Prophylaxis 2 possibilities2 possibilities –Antitoxin Prevents disease if start prior to symptom onsetPrevents disease if start prior to symptom onset –Specific human hyperimmune globulin

53 53 Antitoxin not recommended for PEPAntitoxin not recommended for PEP –Limited supply –Substantial adverse effects –Exposures have variable clinical effects RecommendationRecommendation –Closely monitor known/suspected exposed –treat with antitoxin at first sign of disease Post Exposure Prophylaxis

54 54 Prevention Natural diseaseNatural disease –Boil home-canned foods 10 minutes –Follow USDA instructions on home- canning –Restrict honey from < 1 year old –Seek medical care for wounds –Avoid injectable street drugs

55 55 Prevention VaccineVaccine –Botulinum pentavalent toxoid Not available to general publicNot available to general public Limited supply provided by CDCLimited supply provided by CDC In use for laboratory workers, militaryIn use for laboratory workers, military Protects vs. types A-EProtects vs. types A-E Long-lasting immunityLong-lasting immunity –Prohibits future therapeutic use of toxin Onset too slow to be effective PEPOnset too slow to be effective PEP

56 56 Infection Control Standard precautions onlyStandard precautions only No person-to-person transmissionNo person-to-person transmission

57 57 Decontamination Heat all food 85ºC x 5 minHeat all food 85ºC x 5 min Aerosolized toxin viabilityAerosolized toxin viability –Inactivate by 2 days in optimal conditions Re-aerosolization a theoretical concernRe-aerosolization a theoretical concern Mask over the face may be protectiveMask over the face may be protective Exposed clothing and surfacesExposed clothing and surfaces –Wash with 1:10 hypochlorite solution

58 58 References: 1)Botulism, bioterrorism : Center for the study of bioterrorism and emerging infections, Saint Louis University School of Public Health. 2)Hatami H. : Clinical Epidemiology and Control of Infectious Diseases related to Bioterrorism, Second edition. (http://www.elib.hbi.ir/persian/library.htm) 3)Glenda Dvorak,Botulism, the center for food security & public health, Iowa state university. 4)Vahdani P. Botulism & food borne disease, Shahid Beheshti University of Medical Sciences, 5)Mandell )Harrison )CDC Internet site 8)WHO Internet site


Download ppt "بسم الله الرحمن الرحيم BIODEFENSE Epidemiology of Botulism Shahid Beheshti University of medical sciences, April 2005 By: Vahdani P. MD. MPH, Hatami H."

Similar presentations


Ads by Google