Category	Biologic Agent	Disease
A (highest immediate risk)	Variola major Bacillus anthracis Yersinia pestis Clostridium botulinum (botulinum toxins) Francisella tularensis Filoviruses and arenaviruses (e.g., Ebola virus,   Lassa virus)	Smallpox Anthrax Plague Botulism Tularemia Viral hemorrhagic fevers
B (next highest risk)	Coxiella burnetii Brucella species Burkholderia mallei Burkholderia pseudomallei Alphaviruses (VEE, EEE, WEE) Rickettsia prowazekii Toxins (e.g., ricin, staphylococcal enterotoxin B) Chlamydia psittaci Food-safety threats (e.g., Salmonella species, E. coli 0157:H7) Water-safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum)	Q fever Brucellosis Glanders Melioidosis Encephalitis Typhus fever Toxic syndromes Psittacosis
C (potential, but not immediate, risk)	Emerging-threat agents (e.g., Nipah virus, hantavirus)

EEE - eastern equine encephalitis VEE - Venezuelan equine encephalitis WEE - western equine encephalitis

Presence of a large epidemic Unusually severe disease or unusual routes of exposure Unusual geographic area, unusual season, or absence of normal vector Multiple simultaneous epidemics of different diseases Outbreak of zoonotic disease Unusual strains of organisms or antimicrobial-resistance patterns Higher attack rates in persons with common exposures Credible threat, as determined by authorities, of biologic attack Direct evidence of biologic attack

Incubation Period	Clinical Presentation	Differential Diagnosis	Diagnostic Testing
7-17 days; mean, 10-12 days	Severe, acute febrile prodrome 1-4 days before rash onset, with temperature >/= 101° F (38.3° C), headache, backache, chills, vomitting, abdominal pain, prostration Enanthem on oropharyngeal mucosa, followed by rash on face, forearms, distal extremities, then trunk; lesions most concentrated on face and distal extremities Lesions evolve slowly from macules to papules to deep-seated, firm, nodular, round, well-circumscribed vesicles or pustules to scrabs over 1-2 days per stage; are in same stage of evolution on a given area of the body; may become umbilicated or confluent Hemorrhagic smallpox: bleeding into skin and mucous membranes Flat-type/malignant smallpox: lesions remain soft and flattened, coalesce Modified smallpox: less severe with fewer, more superficial and rapidly evolving lesions	Varicella (chickenpox); disseminated herpes zoster and simplex; drug eruptions; erythema multiforme; enteroviral infections; secondary syphilis; contact dermatitis; impetigo; scabies; molluscum contagiosum Hemorrhagic smallpox: meningococcemia, Rocky Mountan spotted fever, ehrlichiosis, gram-negative bacterial sepsis, severe acute leukemia Malignant smallpox: hemorrhagic chickenpox	Diagnostic testing at BSL-4 laboratory, including skin biopsy, electron microscopic examination of vesicular and pustular fluid, culture, PCR; serology Appropriate infection control precautions

Note: The clinical manifestations of infections acquired during a biologic attack may differ from those of naturally occurring infections. Clinicians should remain alert for compatible syndromes that vary from the descriptions given.
BSL-4 - biosafety level 4
PCR - polymerase chain reaction

Clinical Feature	Smallpox	Chickenpox
Prodromal illness	Febrile prodrome lasting 1-4 days; patient appears ill or toxic	No or mild prodrome; patients typically do not appear ill
Appearance of lesions	Firm, round, well-circumscribed, deep-seated lesions; may be umbilicated	Superficial lesions
Stage of lesions on any one part of the body	Lesions are all at the same stage of development on a given area of the body	Lesions occur in crops with various stages of development evident on a given area of the body
Initial lesions	Oral mucosa, face, or forearms	Face, then trunk
Oral lesions	Early; may not be evident	May occur
Severity of illness	Typically severe	Typically not severe
Distribution of rash	Centrifugal: lesions concentrated on the face and extremities, with relative sparing of the trunk	Centripetal: lesions concentrated on the trunk with relative sparing of the face and extremities
Lesions on palms or soles	Lesions on palms and soles in majority of cases	Lesions on palms and soles uncommon
Rate of evolution of rash	Slow evolution of lesions from macules to papules to pustules over days	Rapid evolution from macules to papules to crusted lesions within 24 hours
Presence of pruritus	Lesions may be painful and are not usually pruritic until scabbing occurs	Often pruritic, typically not painful in the absence of secondary infection
Hemorrhagic lesions	Can occur	Can occur

Patients	Medication and Dosage	Comments
Adults, including pregnant women and immunocompromised persons	Ciprofloxacin, 400 mg I.V., q. 12 hr or Doxycycline, 100 mg I.V., q. 12 hr and One or two additional antimicrobials*	If meningitis is suspected, doxycycline may be less optimal because of poor central nervous system penetration Modify regimen on the basis of susceptibility testing of isolate; can switch to p.o. after patient is clinically stable; continue treatment for at least 60 days Consider corticosteroids for meningitis, severe edema, or respiratory compromise
Children, including those who are immunocompromised	Ciprofloxacin, 10-15 mg/kg I.V., q. 12 hr, not to exceed 1 g/day or Doxycycline If </= 8 yr and </= 45 kg, give adult dosage If </= 8 yr or if > 8 yr but </= 45 kg, give 2.2 mg/kg q. 12 hr (maximum, 200 mg/day) and One or two additional antimicrobials*	If meningitis is suspected, doxycycline may be less optimal because of poor central nervous system penetration Modify regimen on the basis of susceptibility testing of isolate; can switch to p.o. after patient is clinically stable; continue treatment for at least 60 days Consider corticosteroids for meningitis, severe edema, or respiratory compromise

Note: Treatment recommendations may change over time and according to antimicrobial susceptibility test results during a biologic attack and to availability of selected antimicrobial agents. Before initiating treatment, clinicians should consult with an infectious disease specialist and public health authorities and should check for revisions and updates at http://www.bt.cdc.gov/HealthProfessionals/index.asp. This information is adapted from CDC and Working Group on Civilian Biodefense recommendations and may not represent FDA-approved uses.
*Other agents with in vitro activity anthrax include rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin.

Patients	Medication	Comments
Adults, including immunocompromised persons	Ciprofloxacin, 500 mg p.o., q. 12 hr or Doxycycline, 100 mg p.o., q. 12 hr or, if strain proved susceptible, Amoxicillin, 500 mg p.o., q. 8 hr	Give prophylaxis for at least 60 days
Pregnant women	Ciprofloxacin, 500 mg p.o., q. 12 hr or, if strain proved susceptible, Amoxicillin, 500 mg p.o., q. 8 hr	Give prophylaxis for at least 60 days
Children, including those   who are immunocompromised	Ciprofloxacin, 10-15 mg/kg p.o., b.i.d., not to exceed 1g/day or, if strain proved susceptible, Amoxicillin If 3 20 kg: 500 mg p.o., q. 8 hr If < 20 kg: 80 mg/kg/day p.o., in divided doses q. 8 hr (maximum, 500 mg/dose)	Give prophylaxis for at least 60 days

Note: Prophylaxis recommendations may change over time and according to antimicrobial susceptibility test results during a biologic attack and to availability of selected antimicrobial agents. Before initiating prophylaxis, clinicians should consult with an infectious disease specialist and public health authorities and should check for revisions and updates at http://www.bt.cdc.gov/HealthProfessionals/index.asp. This information is adapted from CDC and Working Group on Civilian Biodefense recommendations and may not represent FDA-approved uses.

Patients	Drug	Comments
Adults	Streptomycin, 1 g I.M., b.i.d. or Gentamicin, 5 mg/kg I.M. or I.V., q.d., or 2 mg/kg loading dose followed by 1.7 mg/kg I.M. or I.V., t.i.d. Alternative choices: Doxycycline, 100 mg I.V., b.i.d., or 200 mg I.V., q.d. Ciprofloxacin, 400 mg I.V., b.i.d. Chloramphenicol, 25 mg/kg I.V., q.i.d.	Treat for 10 days; during a community outbreak of pneumonic plague, all persons developing a temperature >/= 101.3° F (38.5° C) or greater or a new cough should begin parenteral antibiotic treatment; oral treatment may be given when resources for parenteral treatment are limited; pregnant women should not receive streptomycin or chloramphenicol; tetracycline may be substituted for doxycycline
Children	Streptomycin, 15 mg/kg I.M., b.i.d. (maximum, 2 g/day) or Gentamicin, 2.5. mg/kg I.M. or I.V., t.i.d. Alternative choices: Doxycycline: if >/= 45 kg, adult dosage; if < 45 kg, 2.2 mg/kg b.i.d. (maximum, 200 mg/day) Ciprofloxacin, 15 mg/kg I.V., b.i.d. Chloramphenicol, 25 mg/kg I.V., q.i.d.; maintain serum concentration between 5 and 20 µg/ml	Use chloramphenicol in plague meningitis

Note: Treatment recommendations may change over time and according to antimicrobial susceptibility test results during a biologic attack and to availability of selected antimicrobial agents. Before initiating treatment, clinicians should consult with an infectious disease specialist and public health authorities and should check for revisions and updates at http://www.bt.cdc.gov/HealthProfessionals/index.asp. This information is adapted from CDC and Working Group on Civilian Biodefense recommendations and may not represent FDA-approved uses.

Patients	Drug	Comments
Adults, including pregnant women	Doxycycline, 100 mg p.o., b.i.d. Ciprofloxacin, 500 mg p.o., b.i.d. Alternative: Chloramphenicol, 25 mg/kg p.o., q.i.d.	Asymptomatic household contacts, hospital contacts, or other close contacts should receive postexposure prophylaxis for 7 days; contacts who develop fever or cough while receiving prophylaxis should begin antibiotic treatment for plague.
Children	Doxycycline: if >/= 45 kg, adult dosage; if < 45 kg, 2.2 mg/kg p.o., b.i.d. (maximum, 200 mg/day) Ciprofloxacin, 20 mg/kg p.o., b.i.d. Alternative: Chloramphenicol, 25 mg/kg p.o., q.i.d.	Asymptomatic household contacts, hospital contacts, or other close contacts should receive postexposure prophylaxis for 7 days; contacts who develop fever or cough while receiving prophylaxis should begin antibiotic treatment for plague.

Note: Prophylaxis recommendations may change over time and according to antimicrobial susceptibility test results during a biologic attack and to availability of selected antimicrobial agents. Before initiating prophylaxis, clinicians should consult with an infectious disease specialist and public health authorities and should check for revisions and updates at http://www.bt.cdc.gov/HealthProfessionals/index.asp. This information is adapted from CDC and Working Group on Civilian Biodefense recommendations and may not represent FDA-approved uses.