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Bioterrorism TABLE 3 S. Class A Bioterrorism Agents Disease-Agent lncubationPeriod ClinicalFeatures Treatment Prophylaxis Anthrax-Bacillus 1-60 days lnhalational: malaise, Ciprofloxaci n, levofloxaci n, Ciprofloxacin, anthracis fever, myalgia, cough, moxifloxacin, or doxycycline levofloxacin, dyspnea, substernal plus one ortwo additional moxifloxacin, or chest discomfoft, agentsa for 60 days doxycycline, along respiratory distress with vaccinationc Consider raxibacumab, Cutaneous: necrotic obiltoxaximab, or intravenous Amoxicillin if eschar anthrax immune globulinb penicillin-sensitive straind Gastrointestinal: distention, peritonitis Raxibacumab or obiltoxaximab' Smallpox virus-variola 7 -17 days Feverfollowed by Tecovirimat (approved in the Vaccine if exposure VITUS pustular cutaneous rash event of a potential outbreak) occurred in the (face, followed by upper previous 7 days extremities, lower extrem ities, and tru n k); lesions evolve synchronously (same stage of maturation on any one area ofthe body) from macules to papules to vesicles to pustules before eventually crusting Plague-Yersinla pestis 1-6 days Fulminant pneumonia Streptomycin or gentamicin for Doxyrycline or and sepsis 7 to 10 days levofloxacin for 7 days Lymphadenopathy Chloramphenicolr (buboes), fever, rigors, and headache in bubonic Alternatives: doxycycline or levofl oxacin if aminoglycosides plague contraindicated Botulism-Clostridium 2 hours to 8 days Cranial nerye palsies and Antitoxin (HBAT)g and Antibotulinum botulinum symmetric descending supportive care antitoxin (equine flaccid paralysis with serum heptavalent prominent bulbar signs botulism toxin) (the "4 Ds" of diplopia, dysa rthria, dysphonia, and dysphagia), which may progress to respiratory failure Tu la rem ia- Fra nci sel I a 3-5 days Abrupt onset fever, Streptomycin or gentamicin Doxycycline or tularensis respiratory distress, and (severe disease) for 7 to 14 days ciprofloxacin for sepsis 1 4 days Chloramphenicolr Doxycycl i ne or ciprofloxacin (nonsevere disease)for 14 days Viral hemorrhagic Variable Maculopapular rash, Supportive care Vaccine (strictly for fevers-Ebola and fevel headache, myalgia, Zaire ebolavirus) Marburg viruses abdominalpain, Experimental a ntiviral diarrhea, unexplained medications bleeding and bruising; progression leads to shock, hemorrhage, and multiorgan failure

TABLE 3 S. Class A Bioterrorism Agents Disease-Agent lncubationPeriod ClinicalFeatures Treatment Prophylaxis Anthrax-Bacillus 1-60 days lnhalational: malaise, Ciprofloxaci n, levofloxaci n, Ciprofloxacin, anthracis fever, myalgia, cough, moxifloxacin, or doxycycline levofloxacin, dyspnea, substernal plus one ortwo additional moxifloxacin, or chest discomfoft, agentsa for 60 days doxycycline, along respiratory distress with vaccinationc Consider raxibacumab, Cutaneous: necrotic obiltoxaximab, or intravenous Amoxicillin if eschar anthrax immune globulinb penicillin-sensitive straind Gastrointestinal: distention, peritonitis Raxibacumab or obiltoxaximab' Smallpox virus-variola 7 -17 days Feverfollowed by Tecovirimat (approved in the Vaccine if exposure VITUS pustular cutaneous rash event of a potential outbreak) occurred in the (face, followed by upper previous 7 days extremities, lower extrem ities, and tru n k); lesions evolve synchronously (same stage of maturation on any one area ofthe body) from macules to papules to vesicles to pustules before eventually crusting Plague-Yersinla pestis 1-6 days Fulminant pneumonia Streptomycin or gentamicin for Doxyrycline or and sepsis 7 to 10 days levofloxacin for 7 days Lymphadenopathy Chloramphenicolr (buboes), fever, rigors, and headache in bubonic Alternatives: doxycycline or levofl oxacin if aminoglycosides plague contraindicated Botulism-Clostridium 2 hours to 8 days Cranial nerye palsies and Antitoxin (HBAT)g and Antibotulinum botulinum symmetric descending supportive care antitoxin (equine flaccid paralysis with serum heptavalent prominent bulbar signs botulism toxin) (the "4 Ds" of diplopia, dysa rthria, dysphonia, and dysphagia), which may progress to respiratory failure Tu la rem ia- Fra nci sel I a 3-5 days Abrupt onset fever, Streptomycin or gentamicin Doxycycline or tularensis respiratory distress, and (severe disease) for 7 to 14 days ciprofloxacin for sepsis 1 4 days Chloramphenicolr Doxycycl i ne or ciprofloxacin (nonsevere disease)for 14 days Viral hemorrhagic Variable Maculopapular rash, Supportive care Vaccine (strictly for fevers-Ebola and fevel headache, myalgia, Zaire ebolavirus) Marburg viruses abdominalpain, Experimental a ntiviral diarrhea, unexplained medications bleeding and bruising; progression leads to shock, hemorrhage, and multiorgan failure chloramphenicol intravenously lor22 weeks (same in pregnant *orn.n). bTogether with antimicrobial agents.

TABLE 3 S. Class A Bioterrorism Agents Disease-Agent lncubationPeriod ClinicalFeatures Treatment Prophylaxis Anthrax-Bacillus 1-60 days lnhalational: malaise, Ciprofloxaci n, levofloxaci n, Ciprofloxacin, anthracis fever, myalgia, cough, moxifloxacin, or doxycycline levofloxacin, dyspnea, substernal plus one ortwo additional moxifloxacin, or chest discomfoft, agentsa for 60 days doxycycline, along respiratory distress with vaccinationc Consider raxibacumab, Cutaneous: necrotic obiltoxaximab, or intravenous Amoxicillin if eschar anthrax immune globulinb penicillin-sensitive straind Gastrointestinal: distention, peritonitis Raxibacumab or obiltoxaximab' Smallpox virus-variola 7 -17 days Feverfollowed by Tecovirimat (approved in the Vaccine if exposure VITUS pustular cutaneous rash event of a potential outbreak) occurred in the (face, followed by upper previous 7 days extremities, lower extrem ities, and tru n k); lesions evolve synchronously (same stage of maturation on any one area ofthe body) from macules to papules to vesicles to pustules before eventually crusting Plague-Yersinla pestis 1-6 days Fulminant pneumonia Streptomycin or gentamicin for Doxyrycline or and sepsis 7 to 10 days levofloxacin for 7 days Lymphadenopathy Chloramphenicolr (buboes), fever, rigors, and headache in bubonic Alternatives: doxycycline or levofl oxacin if aminoglycosides plague contraindicated Botulism-Clostridium 2 hours to 8 days Cranial nerye palsies and Antitoxin (HBAT)g and Antibotulinum botulinum symmetric descending supportive care antitoxin (equine flaccid paralysis with serum heptavalent prominent bulbar signs botulism toxin) (the "4 Ds" of diplopia, dysa rthria, dysphonia, and dysphagia), which may progress to respiratory failure Tu la rem ia- Fra nci sel I a 3-5 days Abrupt onset fever, Streptomycin or gentamicin Doxycycline or tularensis respiratory distress, and (severe disease) for 7 to 14 days ciprofloxacin for sepsis 1 4 days Chloramphenicolr Doxycycl i ne or ciprofloxacin (nonsevere disease)for 14 days Viral hemorrhagic Variable Maculopapular rash, Supportive care Vaccine (strictly for fevers-Ebola and fevel headache, myalgia, Zaire ebolavirus) Marburg viruses abdominalpain, Experimental a ntiviral diarrhea, unexplained medications bleeding and bruising; progression leads to shock, hemorrhage, and multiorgan failure chloramphenicol intravenously lor22 weeks (same in pregnant *orn.n). bTogether with antimicrobial agents. 'Three subcutaneous doses (0, 2, and 4 weeks) of anthrax vaccine absorbed (AVA) <10 days after exposure (same antimicrobials and vaccine in pregnant women). dlf first-line agents are not available or tolerated.

chloramphenicol intravenously lor22 weeks (same in pregnant *orn.n). bTogether with antimicrobial agents. 'Three subcutaneous doses (0, 2, and 4 weeks) of anthrax vaccine absorbed (AVA) <10 days after exposure (same antimicrobials and vaccine in pregnant women). dlf first-line agents are not available or tolerated. "When alternative preventive therapies are not available or are not appropriate. rFor suspected or proven meningitis for 14-21 days. gAvailable from the CDC through local State Health Departments. 58

Bioterrorism likely scenarios for bioterrorism. Patients with suspected pneu- monic plague require droplet precautions. Chest radiographs are nonspecific. Gram stain and cultures of sputum and blood (performed using the highest level biosafety procedures) are often diagnostic. Clinical features and treatment are outlined in Table 38. Untreated, pneumonic plague is uniformly fatal. Asymptomatic persons exposed to aerosolized Y. pestis and close contacts of infected patients within the previous 7 days warrant postexpo- sure prophylaxis. A live attenuated vaccine with protection from respiratory challenge is under investigation. rEY POITIS o Primary pneumonic plague occurs after Yersinia pestis exposure through infectious aerosols and person-to- person transmission through respiratory droplets, FIG U R E 2 8. Diffuse synchronous skin lesions of smallpox. ln the ordinary form which are likely scenarios for bioterrorism. of smallpox, lesions usually appear at the same stage simultaneously in any given part of the body and evolve from macules to papules to pustules and finally to scabs . Asymptomatic persons exposed to aerosolizedYersinia after about 8 days. pestis and close contacts of infected patients within the previous 7 days warrant postexposure prophylaxis with Secondary viremia occurs 1 week later, accompanied by levofl oxacin or doxycycline. fever, systemic symptoms, and rash, beginning with lesions on the oral mucosa and face and then the arms, legs, hands and feet, and to a lesser extent the trunk (tr'igure 28). Patients Botulism remain contagious until all scabs and crusts are shed. Mortality Botulism may spread in a bioterrorism attack through inhala ranges from 15% to 50'X,. tion or ingestion of botulinum neurotoxin after deliberate Treatment is listed in Table 38. Vaccination should be aerosol release or purposeful food contamination. Clinical provided to close contacts. Intravenous vaccinia immune glob- features are described in Table 38. Patients remain afebrile and ulin is indicated in certain vaccinia related complications or mental status remains normal, but nausea, abdominal pain, when vaccination is contraindicated. and dry mouth often accompany the paralysis. Autonomic I(EY POI ]IT dysfunction may also occur. . Smallpox viremia results in fever and systemic symp- Diagnosis depends on identifying the toxin from serum, vomitus, stool, gastric contents, or foods. Treatment toms, followed by lesions on the oral mucosa, then the is supportive (see Table 3B). Heptavalent antitoxin should be face, and then the arms, legs, hands and feet, and to a obtained from the CDC and administered promptly but will lesser extent the trunk. not reverse existent paralysis. Antibiotics are not useful. rET PO I l{T Plague o Botulism treatment includes supportive care and early Primary pneumonic plague occurs after Yersinia pestis administration of antitoxin, although this will not (Figure 29) exposure through infectious aerosols and person-to- reverse existent paralysis. person transmission through respiratory droplets, which are

likely scenarios for bioterrorism. Patients with suspected pneu- monic plague require droplet precautions. Chest radiographs are nonspecific. Gram stain and cultures of sputum and blood (performed using the highest level biosafety procedures) are often diagnostic. Clinical features and treatment are outlined in Table 38. Untreated, pneumonic plague is uniformly fatal. Asymptomatic persons exposed to aerosolized Y. pestis and close contacts of infected patients within the previous 7 days warrant postexpo- sure prophylaxis. A live attenuated vaccine with protection from respiratory challenge is under investigation. rEY POITIS o Primary pneumonic plague occurs after Yersinia pestis exposure through infectious aerosols and person-to- person transmission through respiratory droplets, FIG U R E 2 8. Diffuse synchronous skin lesions of smallpox. ln the ordinary form which are likely scenarios for bioterrorism. of smallpox, lesions usually appear at the same stage simultaneously in any given part of the body and evolve from macules to papules to pustules and finally to scabs . Asymptomatic persons exposed to aerosolizedYersinia after about 8 days. pestis and close contacts of infected patients within the previous 7 days warrant postexposure prophylaxis with Secondary viremia occurs 1 week later, accompanied by levofl oxacin or doxycycline. fever, systemic symptoms, and rash, beginning with lesions on the oral mucosa and face and then the arms, legs, hands and feet, and to a lesser extent the trunk (tr'igure 28). Patients Botulism remain contagious until all scabs and crusts are shed. Mortality Botulism may spread in a bioterrorism attack through inhala ranges from 15% to 50'X,. tion or ingestion of botulinum neurotoxin after deliberate Treatment is listed in Table 38. Vaccination should be aerosol release or purposeful food contamination. Clinical provided to close contacts. Intravenous vaccinia immune glob- features are described in Table 38. Patients remain afebrile and ulin is indicated in certain vaccinia related complications or mental status remains normal, but nausea, abdominal pain, when vaccination is contraindicated. and dry mouth often accompany the paralysis. Autonomic I(EY POI ]IT dysfunction may also occur. . Smallpox viremia results in fever and systemic symp- Diagnosis depends on identifying the toxin from serum, vomitus, stool, gastric contents, or foods. Treatment toms, followed by lesions on the oral mucosa, then the is supportive (see Table 3B). Heptavalent antitoxin should be face, and then the arms, legs, hands and feet, and to a obtained from the CDC and administered promptly but will lesser extent the trunk. not reverse existent paralysis. Antibiotics are not useful. rET PO I l{T Plague o Botulism treatment includes supportive care and early Primary pneumonic plague occurs after Yersinia pestis administration of antitoxin, although this will not (Figure 29) exposure through infectious aerosols and person-to- reverse existent paralysis. person transmission through respiratory droplets, which are Tularemia Francisella tularensis is transmitted by vectors, direct animal contact, and inhalation; person-to-person spread does not occur. Chest radiographs demonstrate infiltrates, hilar lym- phadenopathy, and pleural effusions. Rapid diagnosis relies on a good history and serologic, immunohistochemical, and PCR testing; culture of tissues and fluids is low yield and potentially dangerous to laboratory personnel. Treatment is noted in Table 38. Death occurs in less than 4% of treated patients, but mortality rates reach 30",1, in F lG U R E 29 . This Wright Giemsa stain shows Yersinla pestis,a gram negative untreated pneumonic or typhoidal tularemia. No vaccine is coccobaciIIus with a "safety-pin" appearance (bipolar staining pattern). available.

Tularemia Francisella tularensis is transmitted by vectors, direct animal contact, and inhalation; person-to-person spread does not occur. Chest radiographs demonstrate infiltrates, hilar lym- phadenopathy, and pleural effusions. Rapid diagnosis relies on a good history and serologic, immunohistochemical, and PCR testing; culture of tissues and fluids is low yield and potentially dangerous to laboratory personnel. Treatment is noted in Table 38. Death occurs in less than 4% of treated patients, but mortality rates reach 30",1, in F lG U R E 29 . This Wright Giemsa stain shows Yersinla pestis,a gram negative untreated pneumonic or typhoidal tularemia. No vaccine is coccobaciIIus with a "safety-pin" appearance (bipolar staining pattern). available. 59