1 بسم الله الرحمن الرحيم biodefense epidemiology of anthrax shahid beheshti...

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بسم الله الرحمن الرحيمبسم الله الرحمن الرحيمBIODEFENSEBIODEFENSEEpidemiology of

AnthraxShahid Beheshti University of

medical sciences, 2007By: Hatami H. MD. MPH

الف ـ مقدمه و معرفي الف ـ مقدمه و معرفي بيماريبيماري

- تعريف و اهميت بهداشتي- تعريف و اهميت بهداشتي11

– عامل يا عوامل اتيولوژيك – عامل يا عوامل اتيولوژيك22

ب ـ اپيدميولوژي توصيفي و ب ـ اپيدميولوژي توصيفي و ((OCCURRENCEOCCURRENCE))وقوعوقوع

ج ـ پيشگيري و كنترلج ـ پيشگيري و كنترل

• Human zoonotic diseaseHuman zoonotic disease– Primarily disease of herbivorous Primarily disease of herbivorous

animalsanimals• Sheep, goats, cattleSheep, goats, cattle• Many large documented epizooticsMany large documented epizootics

– Occasional human diseaseOccasional human disease• Epidemics have occurred but Epidemics have occurred but

uncommonuncommon• Rare in developed worldRare in developed world

- تعريف و اهميت بهداشتي- تعريف و اهميت بهداشتي11

Bioweapon PotentialBioweapon Potential• Many countries have weaponized Many countries have weaponized

anthraxanthrax– Former bioweapon programsFormer bioweapon programs

• U.S.S.R., U.S., U.K., and JapanU.S.S.R., U.S., U.K., and Japan

– Recent bioweapon programsRecent bioweapon programs• IraqIraq

– Attempted uses as bioterrorism agentAttempted uses as bioterrorism agent• WW I: WW I: GermansGermans inoculated Allied livestock inoculated Allied livestock• WW II: WW II: JapaneseJapanese use on prisoners use on prisoners

• Features of anthrax suitable as BT Features of anthrax suitable as BT agentagent

1.1. Spores easily dispersed as aerosolSpores easily dispersed as aerosol

2.2. Moderately infectiousModerately infectious

3.3. High mortality for inhalational (86-100%)High mortality for inhalational (86-100%)

4.4. Fairly easy to obtain, produce and storeFairly easy to obtain, produce and store

Bioweapon PotentialBioweapon Potential

• Aerosol method of deliveryAerosol method of delivery– Most likely method expected in BT attackMost likely method expected in BT attack

– Would cause primarily inhalational diseaseWould cause primarily inhalational disease• Spores reside on particles of 1-5 Spores reside on particles of 1-5 μm sizeμm size• Optimal size for deposition into alveoliOptimal size for deposition into alveoli• Form of disease with highest mortalityForm of disease with highest mortality

– Would infect the largest number of peopleWould infect the largest number of people


• Sverdlovsk, Russia 1979Sverdlovsk, Russia 1979– Accidental release from anthrax Accidental release from anthrax

drying plantdrying plant– 79 human cases79 human cases

• All downwind of plantAll downwind of plant• 68 deaths68 deaths• Some infected with multiples strainsSome infected with multiples strains


• Estimated effects of inhalational Estimated effects of inhalational anthraxanthrax– 100 kg spores released100 kg spores released over city size over city size

of Washington DC of Washington DC • 130,000 – 3 million deaths depending on 130,000 – 3 million deaths depending on

weather conditionsweather conditions

– Economic impactEconomic impact• $26.2 billion/100,000 exposed people$26.2 billion/100,000 exposed people


ب ـ اپيدميولوژي توصيفي و ب ـ اپيدميولوژي توصيفي و وقوع آنتراكسوقوع آنتراكس

((Incubation periodIncubation period)) – دوره نهفتگي – دوره نهفتگي11( ( Natural courseNatural course)) – سير طبيعي – سير طبيعي22 Geographical Geographical)) – انتشار جغرافيائي – انتشار جغرافيائي33

distributiondistribution ) )((Timeline trendTimeline trend)) – روند زماني – روند زماني44 – تاثير سن، جنس، شغل و موقعيت – تاثير سن، جنس، شغل و موقعيت 55

اجتماعياجتماعي Predisposing Predisposing)) – تاثير عوامل مساعد كننده – تاثير عوامل مساعد كننده66

factorsfactors ) ) & Susceptibility & Susceptibility)) – حساسيت و مقاومت – حساسيت و مقاومت77

ResistanceResistance ) ) Secondary attack Secondary attack)) – ميزان حمله هاي ثانويه – ميزان حمله هاي ثانويه88

raterate ) ) – نحوه انتقال و دوره قابليت سرايت – نحوه انتقال و دوره قابليت سرايت99((Mode of transmission & period of communicabilityMode of transmission & period of communicability))

ـ دوره نهفتگي ـ دوره نهفتگي11

• Incubation PeriodIncubation Period– Time from exposure to symptomsTime from exposure to symptoms

– CutaneousCutaneous, 3-10 days, 3-10 days

– Very variable for Very variable for inhalationalinhalational• 2-43 days reported2-43 days reported

• Theoretically may be up to 100 daysTheoretically may be up to 100 days

• Delayed germination of sporesDelayed germination of spores

• Bacillus anthracisBacillus anthracis– Aerobic, Gram positive rodAerobic, Gram positive rod– Long (1-10Long (1-10μm), thin (0.5-2.5μm)μm), thin (0.5-2.5μm)– Forms inert Forms inert sporesspores when exposed to O when exposed to O22

• Infectious form, hardyInfectious form, hardy• Approx 1Approx 1μm in sizeμm in size

– VegetativeVegetative bacillus state in vivo bacillus state in vivo• Result of spore germinationResult of spore germination• Non-infectious, fragileNon-infectious, fragile

• Caused by Caused by Bacillus anthracisBacillus anthracis– Spores found in soil worldwideSpores found in soil worldwide

– عامل يا عوامل اتيولوژيك – عامل يا عوامل اتيولوژيك22

• Environmental SurvivalEnvironmental Survival– Spores are hardySpores are hardy

• Resistant to Resistant to dryingdrying, , boilingboiling <10 minutes <10 minutes• Survive for years in soilSurvive for years in soil• Still viable for decades in perma-frostStill viable for decades in perma-frost

– Favorable soil factors for spore viabilityFavorable soil factors for spore viability• High moistureHigh moisture• Organic content Organic content • Alkaline pHAlkaline pH• High calcium concentrationHigh calcium concentration

• Protective AntigenProtective Antigen– Binds Edema Factor to form Edema ToxinBinds Edema Factor to form Edema Toxin– Facilitates entry of Edema Toxin into cellsFacilitates entry of Edema Toxin into cells

• Edema FactorEdema Factor– Massive edema by increasing intracellular Massive edema by increasing intracellular

cAMPcAMP– Also inhibits neutrophil functionAlso inhibits neutrophil function

• Lethal FactorLethal Factor– Stimulates macrophage release of TNF-Stimulates macrophage release of TNF-α, IL-1βα, IL-1β– Initiates cascade of events leading to sepsisInitiates cascade of events leading to sepsis

PathogenesisPathogenesis• Disease requires Disease requires entry of spores entry of spores into into

bodybody• Exposure does not always cause Exposure does not always cause

diseasedisease– Inoculation doseInoculation dose– Route of entryRoute of entry– Host immune statusHost immune status– May depend on pathogen strain May depend on pathogen strain

characteristicscharacteristics

• Three forms of natural diseaseThree forms of natural disease1.1. InhalationalInhalational

1.1. Rare (<5%)Rare (<5%)2.2. Most likely encountered in bioterrorism eventMost likely encountered in bioterrorism event

2.2. CutaneousCutaneous1.1. Most common (95%)Most common (95%)2.2. Direct contact of spores on skinDirect contact of spores on skin

3.3. GastrointestinalGastrointestinal1.1. Rare (<5%), Rare (<5%), 2.2. IngestionIngestion

• MortalityMortality– Inhalational 86-100% (despite treatment)Inhalational 86-100% (despite treatment)

• Era of crude intensive supportive careEra of crude intensive supportive care

– Cutaneous <5% (treated) – 20% (untreated)Cutaneous <5% (treated) – 20% (untreated)– GI approaches 100%GI approaches 100%

ـ سير طبيعيـ سير طبيعي 2 2

ميزان مرگ ناشي از سياه ميزان مرگ ناشي از سياه زخم گوارشيزخم گوارشي

در موارد اسپوراديك، به در موارد اسپوراديك، به مراتب بيشترمراتب بيشتر

از اپيدمي ها بوده و رقم از اپيدمي ها بوده و رقم % )اسپوراديك( % )اسپوراديك( 6060بيش از بيش از

% % 66در مقايسه با كمتر از در مقايسه با كمتر از )اپيدميك( را تشكيل مي دهد)اپيدميك( را تشكيل مي دهد

موارد اسپوراديك و اپيدميك آنتراكس گوارشي در موارد اسپوراديك و اپيدميك آنتراكس گوارشي در 13331333--8585سال هاي سال هاي

Anthrax Disease Complex Anthrax Disease Complex SummarySummary

GIGI

Papule – Papule – vesicle, edema vesicle, edema

+ eschar+ eschar

ResolveResolveToxic shockToxic shockandand

DeathDeath

HemorrhagicHemorrhagicMeningitisMeningitis

CutaneousCutaneous

InhalationalInhalational

Tracheobronchial Tracheobronchial LymphadenitisLymphadenitis

Mediastinitis, cyanosis,Mediastinitis, cyanosis,stridor, pulmonary stridor, pulmonary

edemaedema

1 - 6 1 - 6 daysdays

ABRUPT ABRUPT ONSETONSET

50%50%

20%20%24 - 36 hours24 - 36 hours

• InhalationalInhalational– Asymptomatic incubation periodAsymptomatic incubation period

• Duration 2-43 days, ~10 days in SverdlovskDuration 2-43 days, ~10 days in Sverdlovsk

– Prodromal phaseProdromal phase• Correlates with germination, toxin productionCorrelates with germination, toxin production• Nonspecific flu-like symptoms Nonspecific flu-like symptoms

– Fever, malaise, myalgiasFever, malaise, myalgias– Dyspnea, nonproductive cough, mild chest discomfortDyspnea, nonproductive cough, mild chest discomfort

• Duration several hours to ~3 daysDuration several hours to ~3 days• Can have transient resolution before next phaseCan have transient resolution before next phase

– Fulminant PhaseFulminant Phase


Clinical FeaturesClinical Features• InhalationalInhalational

– Fulminant PhaseFulminant Phase• Correlates with high-grade bacteremia/toxemiaCorrelates with high-grade bacteremia/toxemia

• Critically IllCritically Ill– Fever, diaphoresisFever, diaphoresis

– Respiratory distress/failure, cyanosisRespiratory distress/failure, cyanosis

– Septic shock, multiorgan failure, DICSeptic shock, multiorgan failure, DIC

• 50% develop hemorrhagic meningitis 50% develop hemorrhagic meningitis – Headache, meningismus, delirium, comaHeadache, meningismus, delirium, coma

– May be most prominent findingMay be most prominent finding

• Usually progresses to death in <36 hrsUsually progresses to death in <36 hrs– Mean time from symptom onset to death ~3 daysMean time from symptom onset to death ~3 days

• Laboratory FindingsLaboratory Findings– Gram positive bacilli in direct blood smearGram positive bacilli in direct blood smear– Electrolyte imbalances commonElectrolyte imbalances common

• Radiographic FindingsRadiographic Findings– Widened mediastinumWidened mediastinum

• Minimal or no infiltratesMinimal or no infiltrates

– Can appear during prodrome phaseCan appear during prodrome phase

Clinical FeaturesClinical Features

• CutaneousCutaneous– Most common areas of exposureMost common areas of exposure

• Hands/armsHands/arms

• Neck/headNeck/head

– Incubation periodIncubation period• 3-5 days typical3-5 days typical

• 12 days maximum12 days maximum


• Cutaneous – progression of Cutaneous – progression of painlesspainless lesions lesionsPapule – pruriticPapule – pruritic

Vesicle/bullaVesicle/bulla

Ulcer – contains organisms, sig. Ulcer – contains organisms, sig. edemaedema

Eschar – black, rarely scarsEschar – black, rarely scars

24-36 24-36 hrshrs

daysdays


• CutaneousCutaneous– Systemic disease may developSystemic disease may develop

• Lymphangitis and lymphadenopathyLymphangitis and lymphadenopathy

• If untreated, can progress to sepsis, deathIf untreated, can progress to sepsis, death


• GastrointestinalGastrointestinal– OropharyngealOropharyngeal

• Oral or esophageal ulcerOral or esophageal ulcer– Regional lymphadenopathyRegional lymphadenopathy– Edema, ascitesEdema, ascites– SepsisSepsis

– AbdominalAbdominal• Early symptoms - nausea, vomiting, Early symptoms - nausea, vomiting,

malaisemalaise• Late - hematochezia, acute abdomen, Late - hematochezia, acute abdomen,

ascitesascites


ـ سير طبيعي ـ سير طبيعي 22)مرور()مرور(

ميزان موارد بدون عالمت )ساب ميزان موارد بدون عالمت )ساب •كلينيكال(كلينيكال(

ميزان موارد حادميزان موارد حاد•ميزان موارد مزمن ميزان موارد مزمن •ميزان موارد بهبودي خودبخوديميزان موارد بهبودي خودبخودي•سير بعدي بيماري با درمان و بدون سير بعدي بيماري با درمان و بدون •

درماندرمانميزان مرتاليتي و مربيديتي ميزان مرتاليتي و مربيديتي •

• Occurs worldwideOccurs worldwide

• Endemic areas - Africa, AsiaEndemic areas - Africa, Asia

• True incidence not knownTrue incidence not known

ـ انتشار ـ انتشار 3 3جغرافيائيجغرافيائي

ـ روند زماني ـ روند زماني44

( ( PandemicsPandemics))پاندمي ها ؟پاندمي ها ؟• ( ( EpidemicsEpidemics)) اپيدمي ها ؟ اپيدمي ها ؟•( ( OutbreaksOutbreaks)) طغيان ها ؟ طغيان ها ؟ •( ( DurationDuration ) )تناوب زماني ؟تناوب زماني ؟•( ( SeasonalitySeasonality))الگوي فصلي ؟الگوي فصلي ؟•سياه زخم حيوانات، در مناطق معتدله، معمولا در فصل زمستان، عارض مي شود سياه زخم حيوانات، در مناطق معتدله، معمولا در فصل زمستان، عارض مي شود •

ـ تاثير سن، جنس ، شغل و ـ تاثير سن، جنس ، شغل و 55موقعيت اجتماعيموقعيت اجتماعي

، ، شيوعشيوع و و بروزبروز بر ميزان بر ميزان تاثير سنتاثير سن• و و بدون عالمتبدون عالمت و و با عالمتبا عالمتموارد موارد مزمنمزمن و احتمال و احتمال خفيفخفيف و و شديدشديد

و مير و ميرمرگمرگشدن و ميزان شدن و ميزان

•All ages and genders affectedAll ages and genders affected بر عوامل مذكور بر عوامل مذكورتاثير جنستاثير جنس• ؟ ؟شغل و موقعيت اجتماعيشغل و موقعيت اجتماعي•

ـ تاثير عوامل مساعد كننده ـ تاثير عوامل مساعد كننده66

عوامل فرهنگي و عقيدتيعوامل فرهنگي و عقيدتي•زمينه هائي نظير ضعف ايمني ، زمينه هائي نظير ضعف ايمني ، •

ابتالء به بيماريهاي سركوبگر ابتالء به بيماريهاي سركوبگر ايمني ، مصرف داروهاي مضعف ايمني ، مصرف داروهاي مضعف

سيستم ايمنيسيستم ايمنياسترس هاي مختلفاسترس هاي مختلف•فقر و بي خانمانيفقر و بي خانماني•

ـ حساسيت و مقاومت در مقابل ـ حساسيت و مقاومت در مقابل 77بيماريبيماري

مقاومت طبيعيمقاومت طبيعي•مصونيت اكتسابي بعد از ابتالءمصونيت اكتسابي بعد از ابتالء•مصونيت اكتسابي بعد از مصونيت اكتسابي بعد از •

واكسيناسيونواكسيناسيون

ـ ميزان حمالت ثانويه ـ ميزان حمالت ثانويه88

ـ منابع و مخازن ، نحوه انتقال ـ منابع و مخازن ، نحوه انتقال 99 بيماري و دوره قابليت سرايتبيماري و دوره قابليت سرايت

آنتراكس آنتراكس ( ( SourceSource))تعريف منبع ؟تعريف منبع ؟•((ReservoirReservoir))تعريف مخزن ؟تعريف مخزن ؟•راه هاي انتقالراه هاي انتقال•

مستقيممستقيم–غير مستقيمغير مستقيم–

P. of P. of))دوره قابليت سرايت ؟دوره قابليت سرايت ؟–communicabilitycommunicability ) )

TransmissionTransmission

• Human casesHuman cases – historical risk – historical risk factors factors – AgriculturalAgricultural

• Exposure to Exposure to livestocklivestock

– OccupationalOccupational• Exposure to Exposure to woolwool and hides and hides

• Woolsorter’s disease = inhalational Woolsorter’s disease = inhalational anthraxanthrax

• Rarely Rarely laboratorylaboratory-acquired-acquired


– No human-to-humanNo human-to-human– Naturally occurring casesNaturally occurring cases

• Skin exposureSkin exposure• IngestionIngestion• Airborne Airborne

– BioterrorismBioterrorism• Aerosol (likely)Aerosol (likely)• Small volume powder (possible)Small volume powder (possible)• Foodborne (unlikely)Foodborne (unlikely)

( تماس مستقيم با حيوانات آلوده.1ــت، 2 ــو، پوسـ ــم، مـ ــا پشـ ــاس بـ ( تمـ

استخوان و ساير فراورده هاي آلوده.اي )آئروسـول( 3 ( استنشـاق افشـانه ـه

آلوده.وده 4 ( خـوردن گوشـت و سـاير مـواد آـل

به باسيل شاربون.ــزش و 5 ــر گ ــرات، در اث ــيله حش ( بوس

انتقـال خـون آلـوده بـه سـايرحيوانات و انسان.

( انتقـال انسـان بـه انسـان از طريـق 6نوعي برس تهيه شده از نخل.

( انتقال جنيني يا در حين زايمان 7

راه هاي انتقالراه هاي انتقال

ج ـ پيشگيري و كنترل ج ـ پيشگيري و كنترل آنتراكسآنتراكس

• Primordial Prevention:Primordial Prevention: “…minimize “…minimize hazards to health”hazards to health”

• Primary Prevention:Primary Prevention: Prevention of disease in “well” Prevention of disease in “well”

individualsindividuals• Secondary Prevention:Secondary Prevention:

Identification and intervention in Identification and intervention in early stages of diseaseearly stages of disease

Tertiary Prevention:Tertiary Prevention: Prevention of further deterioration, Prevention of further deterioration,

reduction in complicationsreduction in complications

ـ پيشگيري سطح او�ل ـ پيشگيري سطح او�ل 11

ـ ارتقــــاء آگاهي هــــاي 1بهداشتي مردم

ـ قطـع زنجـيره انتقـال2ــايل ــزن، وس ــع، مخ )منب

انتقال . . .ــا 3 ــ ــ ــي ب ــ ــ ـ پروفيالكس

ــال، ــ ــ ــازي )فع ــ ــ ايمنسانفعــــــــــــــــــــالي( و

كموپروفيالكسي

• VaccineVaccine– Inactivated, cell-free filtrateInactivated, cell-free filtrate

– Adsorbed onto Al(OH)Adsorbed onto Al(OH)33

– Protective Antigen Protective Antigen

– AdministrationAdministration• Dose scheduleDose schedule

– 0, 2 & 4 wks; 6, 12 & 18 months initial series0, 2 & 4 wks; 6, 12 & 18 months initial series

– Annual boosterAnnual booster

• 0.5 ml SQ 0.5 ml SQ

•VaccineVaccine

EfficacyEfficacy

•>95% protection vs. >95% protection vs. aerosol in animal modelsaerosol in animal models

•>90% vs. >90% vs. cutaneouscutaneous in in humanshumans

–Adverse EffectsAdverse Effects

•>1.6 million doses given to military >1.6 million doses given to military by 4/2000by 4/2000

•No deathsNo deaths

•<10% moderate/severe local <10% moderate/severe local reactionsreactions

–Erythema, edemaErythema, edema

•<1% systemic reactions<1% systemic reactions

–Fever, malaiseFever, malaise

Postexposure ProphylaxisPostexposure Prophylaxis

• Who should receive PEP?Who should receive PEP?– Anyone exposed to anthrax Anyone exposed to anthrax

• Empiric Empiric antibioticantibiotic therapy therapy

• VaccinationVaccination

Not for contacts of cases, unless also Not for contacts of cases, unless also exposedexposed

Postexposure ProphylaxisPostexposure Prophylaxis• Avoid unnecessary antibiotic usageAvoid unnecessary antibiotic usage

– Potential Potential shortagesshortages of those who need them of those who need them– Potential Potential adverse effectsadverse effects

• HypersensitivityHypersensitivity

• Neurological side effects, especially elderlyNeurological side effects, especially elderly

• Bone/cartilage disease in childrenBone/cartilage disease in children

• Oral contraceptive failureOral contraceptive failure

– Future antibiotic Future antibiotic resistanceresistance• Individual’s own floraIndividual’s own flora

• Community resistance patternsCommunity resistance patterns


• Antibiotic therapyAntibiotic therapy– Prompt therapy can improve Prompt therapy can improve

survivalsurvival

– Continue for 60 daysContinue for 60 days• 30-45 days if vaccine 30-45 days if vaccine

administeredadministered


• Antibiotic therapyAntibiotic therapy– Same regimenSame regimen as active treatment as active treatment

• Substituting Substituting oraloral equivalent for IV equivalent for IV

• CiprofloxacinCiprofloxacin 500 mg po bid 500 mg po bid empiricallyempirically

• AlternativesAlternatives– DoxycyclineDoxycycline 100 mg po bid 100 mg po bid– AmoxicillinAmoxicillin 500 mg po tid 500 mg po tid


• Antibiotic therapyAntibiotic therapy– ChildrenChildren

• Same dose adjustments as treatmentSame dose adjustments as treatment

• Weigh benefits vs. risksWeigh benefits vs. risks

• Recommended switch if PCN-Recommended switch if PCN-susceptiblesusceptible

– AmoxicillinAmoxicillin 80 mg/kg/day, max 500 mg 80 mg/kg/day, max 500 mg tidtid

ـ پيشگيري سطح دو�م ـ پيشگيري سطح دو�م 22

ـ تشخيص زودرس1 ـ درمان به موقع2ــه 3 ــان ب ــه درم ــه ب ـ توج

عنــوان پيشــگيري ســطح او�ل و دو�م

• Presumptive diagnosisPresumptive diagnosis– History of possible exposureHistory of possible exposure– Typical signs & symptomsTypical signs & symptoms– Rapidly progressing nonspecific illnessRapidly progressing nonspecific illness– Widened mediastinum on CXRWidened mediastinum on CXR– Large Gram+ bacilli from specimensLarge Gram+ bacilli from specimens

• Can be seen on Gram stain if hi-grade bacteremiaCan be seen on Gram stain if hi-grade bacteremia

– Appropriate colonial morphologyAppropriate colonial morphology– Necrotizing mediastinitis, meningitis at autopsyNecrotizing mediastinitis, meningitis at autopsy

• Definitive diagnosisDefinitive diagnosis– Direct culture on standard blood agarDirect culture on standard blood agar

• Gold standardGold standard, widely available, widely available• Alert labAlert lab to work up Gram + bacilli if found to work up Gram + bacilli if found• 6-246-24 hours to grow hours to grow• SensitivitySensitivity depends on severity, prior antibiotic depends on severity, prior antibiotic

– Blood, fluid from skin lesions, pleural fluid, CSF, Blood, fluid from skin lesions, pleural fluid, CSF, ascitesascites

– Sputum unlikely to be helpful (not a pneumonia)Sputum unlikely to be helpful (not a pneumonia)

• Very high specificity if non-motile, non-hemolyticVery high specificity if non-motile, non-hemolytic• Requires biochemical tests for >99% confirmationRequires biochemical tests for >99% confirmation

– Available at Reference laboratoriesAvailable at Reference laboratories

• Testing for exposureTesting for exposure– Nasal swabsNasal swabs

• Can detect spores prior to illnessCan detect spores prior to illness• Currently used only as epidemiologic toolCurrently used only as epidemiologic tool

– Decision for PEP based on exposure riskDecision for PEP based on exposure risk– May be useful for antibiotic sensitivity in May be useful for antibiotic sensitivity in

exposedexposed

• CultureCulture on standard media on standard media• Swabs of Swabs of naresnares and and facialfacial skin skin

– SerologiesSerologies• May be useful from epidemiologic standpointMay be useful from epidemiologic standpoint

DiagnosisDiagnosis

TestTest AvailabilityAvailability TimeTime SensSens SpecSpec

CultureCulture Most labsMost labs 1-3 1-3 daysdays ModMod HighHigh

Biochemical Biochemical Large labsLarge labs Hours Hours N/A N/A HighHigh

Skin testSkin test None None 1-2 1-2 daysdays HighHigh ??

PCRPCR ReferenceReference Hours Hours HighHigh High High

ELISAELISA ReferenceReference HoursHours Mod Mod High High

Differential DiagnosisDifferential Diagnosis

• InhalationalInhalational– Influenza Influenza

– PneumoniaPneumonia• Community-acquiredCommunity-acquired

• AtypicalAtypical

• Pneumonic tularemiaPneumonic tularemia

• Pneumonic plaguePneumonic plague

– Mediastinitis Mediastinitis

– Bacterial meningitisBacterial meningitis

– Thoracic aortic aneurysmThoracic aortic aneurysm

Expect if anthraxExpect if anthraxFlu rapid diagnostic –Flu rapid diagnostic –

More severe in young ptsMore severe in young pts

No infiltrateNo infiltrate

No prior surgeryNo prior surgery

Bloody CSFBloody CSF

FeverFever


• CutaneousCutaneous– Spider biteSpider bite– Ecthyma Ecthyma

gangrenosumgangrenosum– Pyoderma Pyoderma

gangrenosumgangrenosum– Ulceroglandular Ulceroglandular

tularemiatularemia– Mycobacterial ulcerMycobacterial ulcer– Cellulitis Cellulitis

Expect if Expect if anthraxanthraxfeverfever

no response to 3no response to 3ºº cephscephs

painlesspainless, black eschar, black eschar

+/- lymphadenopathy+/- lymphadenopathy

usually sig. local usually sig. local edemaedema


• GastrointestinalGastrointestinal– GastroenteritisGastroenteritis– Typhoid Typhoid – PeritonitisPeritonitis– Perforated ulcerPerforated ulcer– Bowel obstructionBowel obstruction

Expect if anthraxExpect if anthraxCritically illCritically ill

Acute abdomenAcute abdomen

Bloody diarrheaBloody diarrhea

Fever Fever

TreatmentTreatment• Immediately treat presumptive casesImmediately treat presumptive cases

– Prior to confirmationPrior to confirmation– Rapid antibiotics may improve survivalRapid antibiotics may improve survival

• Differentiate between cases and Differentiate between cases and exposedexposed

– CasesCases• Potentially exposed with any signs/symptomsPotentially exposed with any signs/symptoms

– ExposedExposed• Potentially exposed but asymptomaticPotentially exposed but asymptomatic• Provide Post-Exposure ProphylaxisProvide Post-Exposure Prophylaxis

TreatmentTreatment• HospitalizationHospitalization• IV antibioticsIV antibiotics

– Empiric until sensitivities are Empiric until sensitivities are knownknown

• Intensive supportive careIntensive supportive care– Electrolyte and acid-base Electrolyte and acid-base

imbalancesimbalances– Mechanical ventilationMechanical ventilation– Hemodynamic supportHemodynamic support

• Antibiotic selectionAntibiotic selection– Naturally occurring strainsNaturally occurring strains

• Rare penicillin resistance, but inducible Rare penicillin resistance, but inducible β-lactamaseβ-lactamase

• Penicillins, aminoglycosides, tetracyclines, Penicillins, aminoglycosides, tetracyclines, erythromycin, chloramphenicol have been effectiveerythromycin, chloramphenicol have been effective

• Ciprofloxacin very effective in vitro, animal studiesCiprofloxacin very effective in vitro, animal studies

• Other fluoroquinolones probably effective Other fluoroquinolones probably effective

– Engineered strainsEngineered strains• Known penicillin, tetracycline resistanceKnown penicillin, tetracycline resistance

• Highly resistant strains = mortality of untreatedHighly resistant strains = mortality of untreated

TreatmentTreatment

TreatmentTreatment• Empiric TherapyEmpiric Therapy

– AdultsAdults• Ciprofloxacin 400 mg IV q12Ciprofloxacin 400 mg IV q12°°

OROR

Doxycycline 100mg IV q12Doxycycline 100mg IV q12°°

AND AND (for (for inhalational)inhalational)

One or two other antibioticsOne or two other antibiotics

TreatmentTreatment• Other antibiotic considerationsOther antibiotic considerations

– Other fluoroquinolones possibly equivalentOther fluoroquinolones possibly equivalent– High dose penicillin for 2High dose penicillin for 2ndnd empiric agent empiric agent

• 50% present with meningitis50% present with meningitis

– Clindamycin for severe diseaseClindamycin for severe disease• May reduce toxin productionMay reduce toxin production

– Chloramphenicol for known meningitisChloramphenicol for known meningitis• Penetrates blood brain barrierPenetrates blood brain barrier

TreatmentTreatment• Empiric TherapyEmpiric Therapy

– ChildrenChildren• CiprofloxacinCiprofloxacin 10-15 mg/kg/d IV q12 10-15 mg/kg/d IV q12°, m°, max 1 ax 1

g/dg/d ORORDoxycyclineDoxycycline 2.2 mg/kg IV q12 2.2 mg/kg IV q12°°

(adult dosage if >8 yo and >45 kg)(adult dosage if >8 yo and >45 kg)• Add one or two antibiotics for inhalationalAdd one or two antibiotics for inhalational• Weigh risks (arthropathy, dental enamel)Weigh risks (arthropathy, dental enamel)

• Empiric therapyEmpiric therapy– Pregnant womenPregnant women

• Same as other adultsSame as other adults• Weigh small risks (fetal arthropathy) vs Weigh small risks (fetal arthropathy) vs

benefitbenefit

– ImmunosuppressedImmunosuppressed• same as other adultssame as other adults

TreatmentTreatment

• Alternative antibioticsAlternative antibiotics– If susceptible, or cipro/doxy not possibleIf susceptible, or cipro/doxy not possible

• Penicillin*, amoxicillin Penicillin*, amoxicillin

• Gentamicin, streptomycinGentamicin, streptomycin

• Erythromycin, chloramphenicolErythromycin, chloramphenicol

•Ineffective antibioticsIneffective antibiotics–Trimethoprim/SulfamethoxazoleTrimethoprim/Sulfamethoxazole–Third generation cephalosporinsThird generation cephalosporins

•Ineffective antibioticsIneffective antibiotics–Trimethoprim/SulfamethoxazoleTrimethoprim/Sulfamethoxazole–Third generation cephalosporinsThird generation cephalosporins

TreatmentTreatment

• Antibiotic therapyAntibiotic therapy– DurationDuration

• 60 days60 days– Risk of delayed spore germinationRisk of delayed spore germination– Vaccine availabilityVaccine availability

» Could reduce to 30-45 days therapyCould reduce to 30-45 days therapy» Stop antibiotics after 3Stop antibiotics after 3rdrd vaccine dose vaccine dose

– Switch to oralSwitch to oral– Clinical improvementClinical improvement– Patient able to tolerate oral medicationsPatient able to tolerate oral medications

TreatmentTreatment

• Other therapiesOther therapies– Passive immunizationPassive immunization

• Anthrax immunoglobulin from horse serumAnthrax immunoglobulin from horse serum• Risk of serum sicknessRisk of serum sickness

– AntitoxinAntitoxin• Mutated Protective AntigenMutated Protective Antigen

– Blocks cell entry of toxinBlocks cell entry of toxin– Still immunogenic, could be an alternative vaccineStill immunogenic, could be an alternative vaccine– Animal models promisingAnimal models promising

TreatmentTreatment

Infection ControlInfection Control

• No person to person transmissionNo person to person transmission

• Standard Precautions Standard Precautions

• Laboratory safetyLaboratory safety– Biosafety Level (BSL) 2 PrecautionsBiosafety Level (BSL) 2 Precautions

DecontaminationDecontamination

• Highest risk of infection at initial releaseHighest risk of infection at initial release– Duration of aerosol viabilityDuration of aerosol viability

• Several hours to one day under optimal Several hours to one day under optimal conditionsconditions

• Covert aerosol long dispersed by recognition 1Covert aerosol long dispersed by recognition 1stst casecase

– Risk of secondary aerosolization is lowRisk of secondary aerosolization is low• Heavily contaminated small areas Heavily contaminated small areas

– May benefit from decontaminationMay benefit from decontamination

• Decontamination may not be feasible for large Decontamination may not be feasible for large areasareas


• Skin, clothingSkin, clothing– Thorough washing with soap and waterThorough washing with soap and water– Avoid bleach on skinAvoid bleach on skin

• Instruments for invasive proceduresInstruments for invasive procedures– Sterilize, e.g. 5% hypochlorite solutionSterilize, e.g. 5% hypochlorite solution

• Sporicidal agentsSporicidal agents– Sodium or calcium hypochlorite (bleach)Sodium or calcium hypochlorite (bleach)


• Suspicious letters/packagesSuspicious letters/packages– Do not open or shakeDo not open or shake

– Place in plastic bag or leakproof containerPlace in plastic bag or leakproof container

– If visibly contaminated or container unavailableIf visibly contaminated or container unavailable• Gently cover – paper, clothing, box, trash canGently cover – paper, clothing, box, trash can

– Leave room/area, isolate room from othersLeave room/area, isolate room from others

– Thoroughly wash hands with soap and waterThoroughly wash hands with soap and water

– Report to local security / law enforcementReport to local security / law enforcement

– List all persons in vicinityList all persons in vicinity


• Opened envelope with suspicious substanceOpened envelope with suspicious substance– Gently cover, avoid all contactGently cover, avoid all contact

– Leave room and isolate from othersLeave room and isolate from others

– Thoroughly wash hands with soap and waterThoroughly wash hands with soap and water

– Notify local security / law enforcementNotify local security / law enforcement

– Carefully remove outer clothing, put in plasticCarefully remove outer clothing, put in plastic

– Shower with soap and waterShower with soap and water

– List all persons in areaList all persons in area

Outbreak Investigations 2001Outbreak Investigations 2001• Case definitionsCase definitions

– Confirmed caseConfirmed case• Clinically compatible syndromeClinically compatible syndrome• +culture or 2 +non-culture diagnostics+culture or 2 +non-culture diagnostics

– Presumptive casePresumptive case• Clinically compatible syndromeClinically compatible syndrome• 1 +non-culture diagnostic or confirmed exposure1 +non-culture diagnostic or confirmed exposure

– ExposuresExposures• Confirmed exposureConfirmed exposure

– May be aided by nasal swab cultures, serologyMay be aided by nasal swab cultures, serology

• AsymptomaticAsymptomatic

Anthrax Essential NotesAnthrax Essential Notes• Rapidly fatal flu-like illness in previous healthyRapidly fatal flu-like illness in previous healthy• Widened mediastinum on Chest X-rayWidened mediastinum on Chest X-ray• Painless black skin ulcerPainless black skin ulcer• Non-motile gram positive bacilli in specimensNon-motile gram positive bacilli in specimens• Diagnosis primarily by routine cultureDiagnosis primarily by routine culture• No person-to-person transmissionNo person-to-person transmission• Rx prior to prodrome essential for survivalRx prior to prodrome essential for survival• Empiric therapy – ciprofloxacinEmpiric therapy – ciprofloxacin• Single inhalational case is an emergencySingle inhalational case is an emergency

– Contact Local Health Departments Contact Local Health Departments

كنترل آنتراكسكنترل آنتراكس

ـ مـبارزه ـبا مـنابع و 1مخازن

ــيره 2 ــ ــع زنج ــ ـ قطانتقال

ـ حفظ افراد سالم3


ـ مبارزه با مخازن1شناســــــــائي بيمــــــــاران و •

؟؟ ناقلينايزوله كردن بيماران ؟؟•تجويز آنتي توكسين ؟؟•تـجويز آـنتي بيوتـيك ـبه بيـماران • درمان حالت ناقلي ؟؟•

حيوانات بيمار و ناقل •منابع محيطي ؟؟•


ـ قطع زنجيره انتقال2ــتقيم و • ــاي مسـ تماس هـ

غيرمستقيمآب، غذا و . . . •پوست، مخاط، هوا، . . .•


ـ حفظ افراد سالم3مصونسازي اكتيو•مصونسازي پاسيو•كموپروفيالكسي•

موارد آنتراكس استنشاقي در واقعه بيوتروريستي آمريكا

از از CDCCDCطبـق گـزارش طبـق گـزارش سوم ماه اكتبرسوم ماه اكتبر

ا 8080 مهـر مهـر 1111 ) ) ا ( ـت نوامـبر نوامـبر 1414( ـت( ( 13801380 آبــان مــاه آبــان مــاه 2323 ) )20012001 ـمورد ـسياه زخم در ـمورد ـسياه زخم در 2222تـعداد تـعداد

ارتبـــــــاط بـــــــا حملـــــــه ارتبـــــــاط بـــــــا حملـــــــه بيوتروريســــتي در آمريكــــا بيوتروريســــتي در آمريكــــا ــه ــت، ب ــده اس ــايي ش ــه شناس ــت، ب ــده اس ــايي ش شناس

مـــورد آن مـــورد آن 1818طـــوري كـــه طـــوري كـــه مـــورد مظنـــون مـــورد مظنـــون 44قطعي و قطعي و

نـفر آن ـها ـجان ـخود را نـفر آن ـها ـجان ـخود را 55ـبوده ـبوده از دست داده اند. از دست داده اند.

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