Bioterrorism Bioterrorism DiseasesDiseases

Particularly dangerous Particularly dangerous infectionsinfections

Bioterrorism DiseasesBioterrorism Diseases

Bioterrorism agents can be separated into three categories, depending on how easily they can be spread and the severity of illness or death they cause.

A Category agents are considered the highest risk

B- second highest priority and C Category- agents are those that are

considered emerging threats for disease that could be engineered for mass spread in the future: emerging infectious diseases such as Nipah virus and hantavirus

Use as a biological weapon!!

Toxin from Castor bean

SmallpoxSmallpox

Laboratory criteria for confirmation*Laboratory criteria for confirmation*:: Polymerase chain reaction (PCR) identification Polymerase chain reaction (PCR) identification

of variola DNA in a clinical specimen, of variola DNA in a clinical specimen, OR OR - - Isolation of smallpox (variola) virus from a Isolation of smallpox (variola) virus from a

clinical specimen (WHO Smallpox Reference clinical specimen (WHO Smallpox Reference laboratory or laboratory with appropriate laboratory or laboratory with appropriate reference capabilities) reference capabilities) with with variola PCR variola PCR confirmation.confirmation.

Cutaneous Anthrax

Incubation PeriodUsually an immediate response up to 1 day

Typical Signs/Symptoms

Local skin involvement after direct contact with spores or bacilliLocalized itching followed by 1) papular lesion that turns vesicular and 2) subsequent development of black eschar within 7–10 days of initial lesion

Treatment ( Cutaneous Anthrax Treatment Protocol for specific therapy)

Obtain specimens for culture BEFORE initiating antimicrobial therapy. Do NOT use extended-spectrum cephalosporins or trimethoprim/sulfamethoxazole because anthrax may be resistant to these drugs.

PrecautionsStandard contact precautions. Avoid direct contact with wound or wound drainage.

Inhalation Anthrax

Incubation Period Usually <1 week; may be prolonged for weeks (up to 2 months)

Typical Signs/Symptoms (often biphasic, but symptoms may progress rapidly)

Initial phase Non-specific symptoms :low-grade

fever, nonproductive cough, malaise, fatigue, myalgias, profound sweats, chest discomfort (upper respiratory tract symptoms are rare)

Maybe rhonchi on exam, otherwise normal

Chest X-ray:o mediastinal wideningo pleural effusion (often)o infiltrates (rare)

Subsequent phase 1–5 days after

onset of initial symptoms

May be preceded by 1–3 days of improvement

Abrupt onset of high fever and severe respiratory distress (dyspnea, stridor, cyanosis)

Shock, death within 24–36 hours

Lab diagnostic AnthraxLab diagnostic Anthrax

Coordinate all aspects of testing, packaging, and transporting with public health laboratory/LRN.

Obtain specimens appropriate to system affected: o blood (essential)o throat

Clues to diagnosis Aerobic blood culture

growth of large, gram-positive bacilli provides preliminary identification of Bacillus species.

Gastrointestinal Anthrax

Incubation Period

Usually 1–7 days

TypicalSigns

Initial phase

Nausea, anorexia, vomiting, and fever progressing to severe abdominal pain, hematemesis, and diarrhea that is almost always bloody

Acute abdomen picture with rebound tenderness may develop.

Mesenteric adenopathy on computed tomography (CT) scan likely. Mediastinal widening on chest X-ray has been reported

Subsequent phase

2–4 days after onset of symptoms, ascites develops as abdominal pain decreases.

Shock, death within 2–5 days of onset

Oropharyngeal AnthraxIncubation Period Usually 1–7 days

Typical Signs/Symptoms

Initial phase Fever and marked unilateral or bilateral neck swelling caused by regional lymphadenopathySevere throat pain and dysphagiaUlcers at the base of the tongue, initially edematous and hyperemic

Subsequent phase Ulcers may progress to necrosis Swelling can be severe enough to compromise the airway

 Laboratory Coordinate all of testing, packaging, and transporting with public health laboratory/LRN.Obtain specimens appropriate to system affected:

o-blood (essential)o-throat

Clues to diagnosis Aerobic blood culture growth of large, gram-positive bacilli provides preliminary identification of Bacillus species

TreatmentTreatment TreatmentTreatment:: (Obtain specimens for culture BEFORE (Obtain specimens for culture BEFORE

initiating antimicrobial therapy. initiating antimicrobial therapy. Initiate antimicrobial therapy immediately Initiate antimicrobial therapy immediately

upon suspicion. upon suspicion. Do Do NOTNOT use extended-spectrum use extended-spectrum

cephalosporins or cephalosporins or trimethoprim/sulfamethoxazole because trimethoprim/sulfamethoxazole because anthrax may be resistant to these drugs. anthrax may be resistant to these drugs.

Supportive care including controlling pleural Supportive care including controlling pleural effusionseffusions

PrecautionsPrecautions - - Standard contact precautionsStandard contact precautions

Bubonic PlagueBubonic Plague

PLAGUEPLAGUE

Cutaneouse hemorrhages

Plague SymptomsPlague Symptoms

Acral gangrene

HHemoptysisemoptysis

Case definitionCase definition Regional lymphadenitis (bubonic plague) Regional lymphadenitis (bubonic plague) Septicemia without an evident bubo Septicemia without an evident bubo

(septicemic plague) (septicemic plague) Plague pneumonia, resulting from Plague pneumonia, resulting from

hematogenous spread in bubonic or hematogenous spread in bubonic or septicemic cases (secondary pneumonic septicemic cases (secondary pneumonic plague) or inhalation of infectious droplets plague) or inhalation of infectious droplets (primary pneumonic plague) (primary pneumonic plague)

Pharyngitis and cervical lymphadenitis Pharyngitis and cervical lymphadenitis resulting from exposure to larger infectious resulting from exposure to larger infectious droplets or ingestion of infected tissues droplets or ingestion of infected tissues (pharyngeal plague) (pharyngeal plague)

Laboratory criteria for Laboratory criteria for diagnosisdiagnosis

PresumptivePresumptive Elevated serum antibody titer(s) to Elevated serum antibody titer(s) to Yersinia Yersinia

pestispestis fraction 1 (F1) antigen (without fraction 1 (F1) antigen (without documented fourfold or greater change) in a documented fourfold or greater change) in a patient with no history of plague vaccination or patient with no history of plague vaccination or

Detection of F1 antigen in a clinical specimen Detection of F1 antigen in a clinical specimen by fluorescent assay by fluorescent assay

ConfirmatoryConfirmatory Isolation of Isolation of Y. pestisY. pestis from a clinical specimen or from a clinical specimen or Fourfold or greater change in serum antibody Fourfold or greater change in serum antibody

titer totiter to Y. pestis Y. pestis F1 antigen F1 antigen

Untreated plague can progress Untreated plague can progress to a fulminate illness with a to a fulminate illness with a high risk of mortality. Thus, high risk of mortality. Thus,

early and appropriate antibiotic early and appropriate antibiotic treatment is essentialtreatment is essential..

Historically, streptomycin (15 mg/kg, up Historically, streptomycin (15 mg/kg, up to 1 g intramuscularly every 12 h) has to 1 g intramuscularly every 12 h) has been the drug of choice. However, in the been the drug of choice. However, in the United States, supplies of streptomycin United States, supplies of streptomycin are scarce. are scarce.

Gentamicin has been used successfully in Gentamicin has been used successfully in the treatment of human plague,the treatment of human plague, is is inexpensive, and can be dosed once daily. inexpensive, and can be dosed once daily.

Doxycycline (as dosed for anthrax) is a Doxycycline (as dosed for anthrax) is a recommended alternative in patients who recommended alternative in patients who cannot take aminoglycosides or in the cannot take aminoglycosides or in the event of a mass casualty scenario, making event of a mass casualty scenario, making parenteral therapy unachievable. parenteral therapy unachievable.

TreatmentTreatment Because chloramphenicol attains high CSF Because chloramphenicol attains high CSF

concentrations, it has been used to treat concentrations, it has been used to treat CNS infections associated with plagueCNS infections associated with plague

Trimethoprim-sulfamethoxazole has been Trimethoprim-sulfamethoxazole has been used to treat bubonic plague; however, it used to treat bubonic plague; however, it is not considered first-line therapy. is not considered first-line therapy.

Beta-lactam antibiotics and macrolides Beta-lactam antibiotics and macrolides should not be used. should not be used.

Patients with advanced plague have a Patients with advanced plague have a presentation of typical gram-negative presentation of typical gram-negative sepsis and need antibiotic treatment for sepsis and need antibiotic treatment for 10 days, along with other supportive 10 days, along with other supportive measures.measures.

Streptomycin, Streptomycin, Streptomycin sulfateStreptomycin sulfate AdultAdult

1 g IV/IM q12h for 7-14 d or continue for 1 g IV/IM q12h for 7-14 d or continue for 5-7 d once patient is afebrile; not to 5-7 d once patient is afebrile; not to exceed 2 g/dexceed 2 g/d

PediatricPediatric 20-40 mg/kg/d IM for 7-14 d or until 20-40 mg/kg/d IM for 7-14 d or until

patient is afebrile for 5-7 d; not to exceed patient is afebrile for 5-7 d; not to exceed 0.75-1 g/d0.75-1 g/d

Aminoglycoside antibiotic recommended Aminoglycoside antibiotic recommended when less potentially hazardous when less potentially hazardous therapeutic agents are ineffective or therapeutic agents are ineffective or contraindicated.contraindicated.

Gentamicin (Garamycin)Gentamicin (Garamycin)

Gentamicin (Garamycin) Gentamicin (Garamycin) AdultAdult

2 mg/kg IV loading dose with normal 2 mg/kg IV loading dose with normal renal function; then, 1.7 mg/kg IV renal function; then, 1.7 mg/kg IV q8h for 10 dq8h for 10 d

PediatricPediatric Not establishedNot established

DoxycyclineDoxycycline

Doxycycline (Bio-Tab, Doryx, Doxy, Doxycycline (Bio-Tab, Doryx, Doxy, Vibramycin, Vibra-TabsVibramycin, Vibra-Tabs

Inhibits protein synthesis and thus Inhibits protein synthesis and thus bacterial growth by binding to 30S and bacterial growth by binding to 30S and possibly 50S ribosomal subunits of possibly 50S ribosomal subunits of susceptible bacteria.susceptible bacteria.

AdultAdult 100 mg PO/IV q12h100 mg PO/IV q12h PediatricPediatric <8 years: Not recommended<8 years: Not recommended

>8 years: 2-5 mg/kg/d PO/IV qd or divided >8 years: 2-5 mg/kg/d PO/IV qd or divided bid; not to exceed 200 mg/dbid; not to exceed 200 mg/d

Chloramphenicol (Chloromycetin)Chloramphenicol (Chloromycetin)

Chloramphenicol (Chloromycetin)Chloramphenicol (Chloromycetin) Binds to 50S bacterial ribosomal subunits Binds to 50S bacterial ribosomal subunits

and inhibits bacterial growth by inhibiting and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-protein synthesis. Effective against gram-negative and gram-positive bacteria.negative and gram-positive bacteria.

AdultAdult 500 mg PO/IV q6h500 mg PO/IV q6h PediatricPediatric 50-75 mg/kg/d PO/IV divided q6h50-75 mg/kg/d PO/IV divided q6h

Follow-upFollow-up TransfeTransferr Patients with plague who are critically ill and Patients with plague who are critically ill and

require transfer to another facility should be require transfer to another facility should be transported under strict isolation precautions.transported under strict isolation precautions.

Deterrence/PreventionDeterrence/Prevention Prophylactic antibiotic therapy Prophylactic antibiotic therapy

The CDC recommends short-term prophylactic The CDC recommends short-term prophylactic antibiotic therapy in people who have been antibiotic therapy in people who have been bitten by potentially infected rodent fleas bitten by potentially infected rodent fleas during a plague outbreak. during a plague outbreak.

Prophylactic antibiotic therapy is recommended Prophylactic antibiotic therapy is recommended in persons who have handled an animal known in persons who have handled an animal known to be infected with the plague bacterium. to be infected with the plague bacterium.

Prophylactic antibiotic therapy is recommended Prophylactic antibiotic therapy is recommended in persons who have had close exposure to a in persons who have had close exposure to a person or an animal thought to have pneumonic person or an animal thought to have pneumonic plague. Sulfadoxine prophylaxis has been plague. Sulfadoxine prophylaxis has been effective in outbreaks of pneumoniceffective in outbreaks of pneumonic plague plague

Laboratory criteria for Laboratory criteria for diagnosisdiagnosis

PresumptivePresumptive Elevated serum antibody titer(s) to Elevated serum antibody titer(s) to F. F.

tularensistularensis antigen (without documented antigen (without documented fourfold or greater change) in a patient fourfold or greater change) in a patient with no history of tularemia vaccination or with no history of tularemia vaccination or

Detection of Detection of F. tularensisF. tularensis in a clinical in a clinical specimen by fluorescent assay specimen by fluorescent assay

ConfirmatoryConfirmatory Isolation of Isolation of F. tularensisF. tularensis in a clinical in a clinical

specimen or specimen or Fourfold or greater change in serum Fourfold or greater change in serum

antibody titer to antibody titer to F. tularensisF. tularensis antigen antigen

Case classificationCase classification

ProbableProbable: a clinically compatible : a clinically compatible case with supportive serologic case with supportive serologic results (tularemia agglutination results (tularemia agglutination titer of greater than or equal to titer of greater than or equal to 160 in one or more serum 160 in one or more serum specimens obtained after onset specimens obtained after onset of symptoms) of symptoms) ConfirmedConfirmed: a case : a case that is laboratory confirmed that is laboratory confirmed

Medical care in tularemiaMedical care in tularemia

Medical care in tularemia is directed primarily toward antibiotic eradication of F tularensis. Provide symptomatic and supportive care for accompanying conditions (eg, osteomyelitis, pericarditis, peritonitis) as clinically indicated. Streptomycin is considered the drug of choice (DOC). Less experience has been reported with other aminoglycosides, but gentamicin and amikacin are also effective.

TTularemiaularemia treatment treatment

Chloramphenicol and tetracycline are Chloramphenicol and tetracycline are clinically useful; however, relapse rates clinically useful; however, relapse rates of up to 50% are reported when these of up to 50% are reported when these agents are used. agents are used.

Case reports indicate a potential role for Case reports indicate a potential role for erythromycin or fluoroquinolones erythromycin or fluoroquinolones (ciprofloxacin, levofloxacin); however, (ciprofloxacin, levofloxacin); however, clinical experience and in vitro data clinical experience and in vitro data supporting their usesupporting their use

TTularemiaularemia treatment treatment

In vitro susceptibility data support the In vitro susceptibility data support the possible role of third-generation possible role of third-generation cephalosporins (cefotaxime, ceftriaxone) and cephalosporins (cefotaxime, ceftriaxone) and rifampin. rifampin.

However, failures occur with attempted third-However, failures occur with attempted third-generation therapy, and these agents should generation therapy, and these agents should not be used for known or suspected tularemia. not be used for known or suspected tularemia.

F tularensisF tularensis is naturally resistant to penicillins is naturally resistant to penicillins and first-generation cephalosporinsand first-generation cephalosporins

Clinical descriptionClinical description

Ingestion of botulinum toxin results in Ingestion of botulinum toxin results in an illness of variable severity. an illness of variable severity.

Common symptoms are diplopia, blurred Common symptoms are diplopia, blurred vision, and bulbar weakness. Symmetric vision, and bulbar weakness. Symmetric paralysis may progress rapidly.paralysis may progress rapidly.

Laboratory criteria for diagnosisLaboratory criteria for diagnosis Detection of botulinum toxin in serum, Detection of botulinum toxin in serum,

stool, or patient's food, or stool, or patient's food, or Isolation of Isolation of Clostridium botulinumClostridium botulinum from from

stool stool

TreatmentTreatment

For cases of food-borne botulism, For cases of food-borne botulism, doctors sometimes clear out the doctors sometimes clear out the digestive system by inducing digestive system by inducing vomiting and giving medications to vomiting and giving medications to induce bowel movements. induce bowel movements.

If you have botulism in a wound, a If you have botulism in a wound, a doctor may need to remove infected doctor may need to remove infected tissue surgically. tissue surgically.

AntitoxinAntitoxin

IInjected antitoxin reduces the risk of njected antitoxin reduces the risk of complications. complications.

The antitoxin attaches itself to toxin The antitoxin attaches itself to toxin that's still circulating in bloodstream that's still circulating in bloodstream and keeps it from harming and keeps it from harming thethe nerves. nerves.

The antitoxin cannot, however, reverse The antitoxin cannot, however, reverse any damage that's already been done any damage that's already been done

Botulinum AntitoxinsBotulinum Antitoxins

There are two primary Botulinum Antitoxins There are two primary Botulinum Antitoxins available for treatment of wound and available for treatment of wound and foodborne botulism. Trivalent (A,B,E) foodborne botulism. Trivalent (A,B,E) Botulinum Antitoxin is derived from equine Botulinum Antitoxin is derived from equine sources This antitoxin is available from the sources This antitoxin is available from the local health department via the local health department via the CDC. .

The second antitoxin is The second antitoxin is heptavalent (A,B,C,D,E,F,G) Botulinum Antitoxin which (A,B,C,D,E,F,G) Botulinum Antitoxin which is derived from "despeciated" equine is derived from "despeciated" equine IgG antibodiesantibodies