Portal de Periódicos da CAPES

Confronting Bioterrorism: Physicians on the Front Line

2002; Elsevier BV; Volume: 77; Issue: 7 Linguagem: Inglês

10.4065/77.7.661

1942-5546

Prathibha Varkey, Gregory A. Poland, Franklin R. Cockerill, Thomas F. Smith, Philip T. Hagen,

Viral Infections and Outbreaks Research

The events surrounding September 11, 2001, and its aftermath have compelled the public health and medical community to face the hitherto unfamiliar reality of bioterrorism. Physicians and public health personnel are frontline soldiers in this new form of warfare. This article provides a general overview of the pathophysiology, clinical presentation, diagnosis, and management of patients infected with the 6 highest priority agents that could potentially be used in bioterrorism. The diseases discussed include anthrax, smallpox, tularemia, plague, botulism, and viral hemorrhagic fevers. Despite the unpredictable nature of bioterrorism, disaster preparedness and knowledge of essential diagnostic and epidemiological principles can contribute substantially toward combating this new threat. The events surrounding September 11, 2001, and its aftermath have compelled the public health and medical community to face the hitherto unfamiliar reality of bioterrorism. Physicians and public health personnel are frontline soldiers in this new form of warfare. This article provides a general overview of the pathophysiology, clinical presentation, diagnosis, and management of patients infected with the 6 highest priority agents that could potentially be used in bioterrorism. The diseases discussed include anthrax, smallpox, tularemia, plague, botulism, and viral hemorrhagic fevers. Despite the unpredictable nature of bioterrorism, disaster preparedness and knowledge of essential diagnostic and epidemiological principles can contribute substantially toward combating this new threat. The recent anthrax attacks in the United States have compelled the public health and medical community to face the hitherto unfamiliar reality of bioterrorism. Since September 11, 2001, there have been 18 confirmed cases of intentional anthrax infection, 5 of which were fatal.1Centers for Disease Control and Prevention CDC update: Connecticut anthrax case and today's telebriefing transcript and audio clip, November 21, 2001 [press release].Available at: www.cdc.gov/od/oc/media/pressrel/r011121p.htmGoogle Scholar Agents formerly unfamiliar to today's generation of health care providers are now part of the day-to-day considerations of our health care system. Bioterrorism, however, is not new.2Christopher GW Cieslak TJ Pavlin JA Eitzen Jr, EM Biological warfare: a historical perspective.JAMA. 1997; 278: 412-417Crossref PubMed Google Scholar, 3Zilinskas RA Iraq's biological weapons: the past as future?.JAMA. 1997; 278: 418-424Crossref PubMed Google Scholar The 14th-century siege of Kaffa (now in Ukraine) was aided by an epidemic of plague when the attacking Tatar force catapulted cadavers of plague victims into the city.2Christopher GW Cieslak TJ Pavlin JA Eitzen Jr, EM Biological warfare: a historical perspective.JAMA. 1997; 278: 412-417Crossref PubMed Google Scholar Closer to home, the Rajneesh cult contaminated salad bars across Oregon with Salmonella typhimurium, causing 751 cases of enteritis and 45 hospitalizations in 1984.2Christopher GW Cieslak TJ Pavlin JA Eitzen Jr, EM Biological warfare: a historical perspective.JAMA. 1997; 278: 412-417Crossref PubMed Google Scholar As recently as 1995, the Aum Shinrikyo cult (Japan) attempted to spread terror by means of anthrax, sarin gas, or botulinum toxin on at least 8 different occasions.2Christopher GW Cieslak TJ Pavlin JA Eitzen Jr, EM Biological warfare: a historical perspective.JAMA. 1997; 278: 412-417Crossref PubMed Google Scholar Bioterrorism is the use of biological agents (both infectious agents and the toxins they produce) to intimidate governments or societies on behalf of an ideologic cause.4Huxsoll DL Parrott CD Patrick III, WC Medicine in defense against biological warfare.JAMA. 1989; 262: 677-679Crossref PubMed Scopus (18) Google Scholar Prior to September 11, 2001, bioterrorism had been low on the medical agenda. This was because of a false sense of security, the feeling that defense against such an attack would be difficult and expensive,5Danzig R Berkowsky PB Why should we be concerned about biological warfare?.JAMA. 1997; 278: 431-432Crossref PubMed Google Scholar and the belief that the use of biological agents was morally repugnant and, hence, unthinkable. Concern surrounding bioterrorism has its roots in the relative stability, lethality, easy availability, and potential communicable nature of culprit agents, as well as their possible resistance to known antibiotics.5Danzig R Berkowsky PB Why should we be concerned about biological warfare?.JAMA. 1997; 278: 431-432Crossref PubMed Google Scholar In addition, these agents are odorless, tasteless, and colorless, and diagnosis may take days to weeks, allowing perpetrators to escape. For editorial comment, see page 619. This article provides an overview of the pathophysiology, clinical presentation, and management of patients infected with agents that could potentially be used in bioterrorism and the public health efforts required to prevent and/or contain bioterrorism. Based on the ease of transmission, severity of morbidity and mortality, and likelihood of use, biological agents can be classified into 3 categories6Biological and chemical terrorism: strategic plan for preparedness and response: recommendations of the CDC Strategic Planning Workgroup.MMWR Recomm Rep. 2000; 49: 1-14Google Scholar (Table 1). Given the extent of the topic, this article is limited to the highest priority agents—Category A (Table 2).Table 1Significant Biological Weapons*Adapted from the Recommendations of the Centers for Disease Control and Prevention Strategic Planning Workgroup.6Category A†Easily disseminated or contagious and causes high mortality.Category B‡Moderately easy to disseminate and causes moderate morbidity or mortality.Category C§Easy availability, production, and dissemination, with potential for high morbidity and mortality.Bacillus anthracisCoxiella brunettiNipah virusSmallpox virusBrucella speciesHanta virusesYersinia pestisBurkholderia malleiTickborne hemorrhagic fever virusesClostridium botulinum Alpha viruses Venezuelan encephalomyelitisEastern and Western equine encephalomyelitisTickborne encephalitis virusesFrancisella tularensisRicin toxin from Ricinus communisYellow fever Viral hemorrhagic fevers FilovirusesArenaviruses Epsilon toxin of Clostridium perfringensStaphylococcus enterotoxin B Foodborne and waterborne diseasesSalmonella speciesShigella dysenteriaeEscherichia coli O157:H7Vibrio choleraCryptosporidium parvumMultidrug-resistant tuberculosis* Adapted from the Recommendations of the Centers for Disease Control and Prevention Strategic Planning Workgroup.6Biological and chemical terrorism: strategic plan for preparedness and response: recommendations of the CDC Strategic Planning Workgroup.MMWR Recomm Rep. 2000; 49: 1-14Google Scholar† Easily disseminated or contagious and causes high mortality.‡ Moderately easy to disseminate and causes moderate morbidity or mortality.§ Easy availability, production, and dissemination, with potential for high morbidity and mortality. Open table in a new tab Table 2Summary of Category A Bioterrorism Agents*Ab = antibody; Ag = antigen; AHF = Argentine hemorrhagic fever; CCHF = Congo-Crimean hemorrhagic fever; DIC = disseminated intravascular coagulation; ELISA = enzyme-linked immunosorbent assay; EM = electron microscopy; IFA = immunofluorescent assay; IM = intramuscular; IV = intravenous; PCR = polymerase chain reaction; RFLP = restriction fragment length polymorphism; RT-PCR = reverse transcriptase PCR; RVF = Rift Valley fever.Disease (causatory organism)PresentationTransmissionDiagnostic testIsolation†Data from Miller7 and www.cdc.gov/ncidod/hip/isolat/isolat.htm.Postexposure prophylaxisTreatmentAnthrax (Bacillus anthracis) InhalationFever with chills, malaise, nonproductive cough, nausea, and/or vomiting. May progress rapidly to respiratory failureInhalation of anthrax sporesSputum, blood, and/or cerebrospinal fluid culture; PCRStandardDuration, 60 days or 100 days or 100 days plus anthrax vaccine; ciprofloxacin, 500 mg orally every 12 h or doxycycline, 100 mg orally every 12 h or amoxicillin, 500 mg orally every 8 h if strain is susceptibleCiprofloxacin, 400 mg IV every 12 h or doxycycline, 200-mg IV load followed by 100 mg IV every 12 h and 1 or 2 additional antimicrobials‡Including rifampin, imipenem, vancomycin, chloramphenicol, clindamycin, clarithromycin, or IV penicillin.§Antimicrobial therapy may be switched to ciprofloxacin, 500 mg orally every 12 h, or doxycycline, 100 mg orally every 12 h, once clinically appropriate and is to be continued for 60 days. GastrointestinalFever, abdominal pain, anorexia, nausea, and vomiting. May have hematemesis and bloody diarrheaEating under-cooked, contaminated meatBlood and/or stool culturesStandard CutaneousPruritic macule or papule that progresses to vesicular lesions, which develop into a black eschar with surrounding edemaDirect contact with spores or with infected skin lesionsVesicular fluid, exudate, and/or eschar culture; biopsy of cutaneous lesionStandardAs aboveCiprofloxacin, 500 mg orally every 12 h or doxycycline, 100 mg orally every 12 h; both for a total of 60 days in the setting of a bioterrorism eventSmallpox (variola virus)High fever, myalgia, headache, and maculo-papular rash with centripetal evolution and synchronous onset. It is vesicular at first and then becomes pustularRespiratory droplets, direct contact with skin lesions or secretionsPharyngeal swab and/or scab material EM; ELISA, RFLP analysis, PCR virus characterizationAirborne and contactVaccinia immune globulin (best within 24 h of exposure)Supportive care; cidofovir (proven effectiveness in vitro)Tularemia (Francisella tularensis) Most common syndromesUlceroglandular: Cutaneous papule that becomes pustular and eventually ulcerates; lymphadenopathyTyphoidal: Fever, abdominal pain, diarrhea, vomiting. Other syndromes include oculoglandular and oropharyngeal tularemia and tularemia pneumoniaInoculation of infected body fluids of animals, bites of infected deerflies, ticks, or mosquitoesBlood, sputum, serum culture; EM of tissue; PCR, immuno-blotting, pulsed-field gel electro-phoresisStandardDoxycycline, 100 mg orally every 12 h for 14 days or ciprofloxacin, 500 mg orally every 12 h for 14 daysStreptomycin, 1 g IM every 12 h for 10 days or gentamicin, 5 mg/kg daily IM or IV for 10 daysBotulism (Clostridium botulinum)Acute, afebrile, descending flaccid paralysis usually accompanied by ptosis, blurred vision, dysarthria, dysphonia, and dysphagiaRespiratory droplets, food or wound contaminationSerum, stool, gastric aspirate, vomitus for detection of toxin, and culture; Ag-ELISA; bioassay using mice for toxin analysisStandardPentavalent toxoidAntitoxins, supportive care, ventilatory care if neededPneumonic plague (Yersinia pestis)High fever, cough, hemoptysis, nausea, vomiting, and headache; may rapidly progress to respiratory failureFlea vectors from rodents, respiratory dropletsBlood, sputum, lymph node aspirate Gram or Wright-Giemsa stain; Ag-ELISA in urine, serology for IgM and IgG, IFADropletDoxycycline, 100 mg orally every 12 h for 10 days or ciprofloxacin, 500 mg orally every 12 h for 10 daysStreptomycin, 1 g IM every 12 h for 10 days or gentamicin, 5 mg/kg per day IM or IV for 10 days or gentamicin, 2 mg/kg loading dose followed by 1.7 mg/kg IM or IV every 8 h for 10 daysViral hemorrhagic fever (varies) Varies with virus origin CCHF: Hemorrhagic complications and DICMarburg, Ebola: DIC, maculopapular rashRVF: Hepatitis, retinitisBunya viridae, Flavivirdae: Acute febrile illness, signs of vascular permeabilityDiffers with each viral syndrome. Commonly transmitted through contact with infected animal reservoirs or arthropod vectorsSerum, blood virus isolation; Ag-ELISA, RT-PCR, Ab-ELISAAirborne and contactIsolation precautionsSupportive therapy CCHF/arenavirus: ribavirin, 30 mg/kg IV initial dose, followed by 15 mg/kg IV every 6 h for 4 days and 7.5 mg/kg IV every 8 h for 6 days; convalescent plasma may be useful for AHF, Lassa fever, and CCHF* Ab = antibody; Ag = antigen; AHF = Argentine hemorrhagic fever; CCHF = Congo-Crimean hemorrhagic fever; DIC = disseminated intravascular coagulation; ELISA = enzyme-linked immunosorbent assay; EM = electron microscopy; IFA = immunofluorescent assay; IM = intramuscular; IV = intravenous; PCR = polymerase chain reaction; RFLP = restriction fragment length polymorphism; RT-PCR = reverse transcriptase PCR; RVF = Rift Valley fever.† Data from Miller7Miller JM Agents of bioterrorism: preparing for bioterrorism at the community health care level.Infect Dis Clin North Am. 2001; 15: 1127-1156Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar and www.cdc.gov/ncidod/hip/isolat/isolat.htm.‡ Including rifampin, imipenem, vancomycin, chloramphenicol, clindamycin, clarithromycin, or IV penicillin.§ Antimicrobial therapy may be switched to ciprofloxacin, 500 mg orally every 12 h, or doxycycline, 100 mg orally every 12 h, once clinically appropriate and is to be continued for 60 days. Open table in a new tab Bacillus anthracis is a spore-forming, gram-positive bacillus. The name has its origin in the Greek word for coal, anthrakis, after the characteristic black skin lesion it produces.8Inglesby TV Henderson DA Bartlett JG Working Group on Civilian Biodefense et al.Anthrax as a biological weapon: medical and public health management.JAMA. 1999; 281: 1735-1745Crossref PubMed Scopus (713) Google Scholar Anthrax is primarily a zoonotic disease of sheep and cattle. Spores can remain viable in the soil and infective to grazing livestock for many decades. Humans get infected through skin contact and ingestion or inhalation of spores, typically from infected animals or animal products. Person-to-person transmission has not been documented. In the United States, the annual incidence of anthrax declined from 130 cases annually in the early 1900s to 1 case of cutaneous anthrax between 1993 and 2000. Prior to October 2001, the last case of inhalation anthrax was in 1976.9Advisory Committee on Immunization Practices Use of anthrax vaccine in the United States.MMWR Recomm Rep. 2000; 49: 1-20Google Scholar, 10Human anthrax associated with an epizootic among livestock—North Dakota, 2000.MMWR Morb Mortal Wkly Rep. 2001; 50: 677-680PubMed Google Scholar However, since October 4, 2001, the Centers for Disease Control and Prevention (CDC) has reported 18 confirmed cases of anthrax: 11 cases of inhalation anthrax associated with 5 fatalities and 7 cases of cutaneous anthrax. Sixteen of these cases are consistent with covert exposure to spores along the postal route of letters.1Centers for Disease Control and Prevention CDC update: Connecticut anthrax case and today's telebriefing transcript and audio clip, November 21, 2001 [press release].Available at: www.cdc.gov/od/oc/media/pressrel/r011121p.htmGoogle Scholar, 11From the Centers for Disease Control and Prevention: investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001.JAMA. 2001; 286: 2086-2088Crossref PubMed Scopus (2) Google Scholar Once introduced into the body, the spores are ingested by macrophages and travel to draining lymph nodes, where they germinate to their vegetative bacillary forms. The bacillus then produces an antiphagocytic capsule and 3 proteins: protective antigen, lethal factor, and edema factor. These act in binary combinations to form toxins. Once protective antigen binds to cell receptors, it is cleaved into a smaller fragment that binds with the lethal factor to form lethal toxin and binds to the edema factor to form edema toxin, both of which play key roles in the pathogenesis of the disease.9Advisory Committee on Immunization Practices Use of anthrax vaccine in the United States.MMWR Recomm Rep. 2000; 49: 1-20Google Scholar A total of 95% of naturally occurring human anthrax is cutaneous and occurs when spores encounter traumatized skin. Within 1 to 12 days after exposure to the spores, a susceptible patient develops a pruritic macule or papule. This progresses to a vesicle in 1 to 2 days and is followed by erosion, leaving a necrotic ulcer with a small painless, depressed black eschar (Figure 1). Diagnosis is often confused by its similarity to insect (eg, spider) bites. The patient may also have symptoms of fever, malaise, headache, and lymphadenopathy. The case fatality rate is up to 20% without therapy and less than 1% with antibiotic treatment.12Swartz MN Recognition and management of anthrax—an update [published correction appears in N Engl J Med. 2002;346:634].N Engl J Med. 2001; 345: 1621-1626Crossref PubMed Scopus (296) Google Scholar, 13Franz DR Jahrling PB Friedlander AM et al.Clinical recognition and management of patients exposed to biological warfare agents.JAMA. 1997; 278: 399-411Crossref PubMed Google Scholar This form of anthrax is rare and is the consequence of eating undercooked, contaminated meat. The incubation period varies from 1 to 7 days. Gastrointestinal anthrax is characterized by acute inflammation of the intestinal tract. Symptoms include fever, abdominal pain, anorexia, nausea, and vomiting. Bloody diarrhea and hematemesis frequently accompany the symptoms. The case fatality rate is unclear but is thought to range from 25% to 60%.12Swartz MN Recognition and management of anthrax—an update [published correction appears in N Engl J Med. 2002;346:634].N Engl J Med. 2001; 345: 1621-1626Crossref PubMed Scopus (296) Google Scholar, 13Franz DR Jahrling PB Friedlander AM et al.Clinical recognition and management of patients exposed to biological warfare agents.JAMA. 1997; 278: 399-411Crossref PubMed Google Scholar No cases of gastrointestinal anthrax have been documented in the United States. A potential, rapidly fatal disease, inhalation anthrax occurs from inhalation of anthrax spores. Estimates from primate data suggest that the lethal inhalation dose (dose that would result in the death of 50% of the exposed population) for humans would range from 2500 to 55,000 inhaled anthrax spores. The incubation period varies from 2 to 60 days. This form of anthrax is classically biphasic and starts with nonspecific symptoms of sore throat, mild fever, and muscle aches. Two to 4 days later, abrupt respiratory failure, hemodynamic collapse, and pulmonary edema may follow these symptoms. Up to half the patients may have hemorrhagic meningitis. Patients can have massive lymphadenopathy, leading to a widened mediastinum, as well as pleural effusions and infiltrates detectable by chest radiology (Figure 2). The classic biphasic nature was not seen in the recent US cases. Death usually occurs within 3 days of the onset of symptoms. Although mortality rates of up to 100% have been reported in untreated cases, lower mortality rates (approximately 40% in the recent US cases) have been observed when timely and appropriate antibiotic therapy is provided.12Swartz MN Recognition and management of anthrax—an update [published correction appears in N Engl J Med. 2002;346:634].N Engl J Med. 2001; 345: 1621-1626Crossref PubMed Scopus (296) Google Scholar, 13Franz DR Jahrling PB Friedlander AM et al.Clinical recognition and management of patients exposed to biological warfare agents.JAMA. 1997; 278: 399-411Crossref PubMed Google Scholar The clinical presentation in the most recent outbreak of inhalation anthrax in the United States was notable for fever with chills, malaise or fatigue, minimal or nonproductive cough, nausea and/or vomiting, tachycardia out of proportion to the fever, and a progressive (ie, not biphasic) clinical course.14Jernigan JA Stephens DS Ashford DA et al.Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States.Emerg Infect Dis. 2001; 7: 933-944Crossref PubMed Scopus (820) Google Scholar, 15Mayer TA Bersoff-Matcha S Murphy C et al.Clinical presentation of inhalational anthrax following bioterrorism exposure: report of 2 surviving patients.JAMA. 2001; 286: 2549-2553Crossref PubMed Scopus (93) Google Scholar, 16Borio L Frank D Mani V et al.Death due to bioterrorism-related inhalational anthrax: report of 2 patients.JAMA. 2001; 286: 2554-2559Crossref PubMed Scopus (150) Google Scholar Laboratory investigations were notable for leukocytosis, elevated serum transaminase levels, and abnormal chest radiographic or computed tomographic findings with a widened mediastinum consistent with lymphadenopathy. With multidrug therapy and supportive care, these patients had a remarkably high survival rate of 60%.14Jernigan JA Stephens DS Ashford DA et al.Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States.Emerg Infect Dis. 2001; 7: 933-944Crossref PubMed Scopus (820) Google Scholar Nasal swabs may be useful for epidemiological purposes but should not be relied on for diagnostic or therapeutic decisions. Relevant to investigations of the recent anthrax outbreak, a confirmed case of anthrax was defined by the CDC11From the Centers for Disease Control and Prevention: investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001.JAMA. 2001; 286: 2086-2088Crossref PubMed Scopus (2) Google Scholar as “(1) a clinically compatible case of cutaneous, inhalational, or gastrointestinal illness … that is laboratory confirmed by isolation of the B. anthracis from an affected tissue or site or (2) other laboratory evidence of B. anthracis infection based on at least two supportive laboratory tests.” The CDC11From the Centers for Disease Control and Prevention: investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001.JAMA. 2001; 286: 2086-2088Crossref PubMed Scopus (2) Google Scholar defines a suspected case of anthrax as “(1) a clinically compatible case of illness without isolation of B. anthracis and no alternative diagnosis, but with laboratory evidence of B. anthracis by one supportive laboratory test or (2) a clinically compatible case of anthrax epidemiologically linked to a confirmed environmental exposure, but without corroborative laboratory evidence of B. anthracis infection.” Laboratory criteria for diagnosis of anthrax consists of isolation and confirmation of B anthracis from a clinical specimen collected from an affected site or other supportive laboratory tests, such as polymerase chain reaction (PCR) evidence, demonstrating the bacterium in a clinical specimen by immunohistochemical staining or serologic testing or other tests that may be validated by laboratory confirmation. Culture may be obtained from blood, stool, cerebrospinal fluid, vesicular fluid, exudate, and eschar specimens or biopsy speci mens of the cutaneous lesion. The colonies are nonpigmented and nonmucoid and have a unique curled hair or “Medusa head” appearance. These bacteria are nonmotile and on sheep agar are nonhemolytic. Although community laboratories can provide presumptive identification of B anthracis by using conventional staining and culture-based methods, confirmation and susceptibility testing is required testing at public health or reference laboratories. Once diagnosed, standard precautions suffice for patients with anthrax. Standard precautions include routine use of gloves for contact with nonintact skin, including any rash or skin lesions. In the event of suspected exposure, thorough washing of skin and clothing with soap and water and decontamination of exposed surfaces with bleach should be done. Anthrax Vaccine Adsorbed, produced from an inactivated cell-free filtrate of an avirulent strain of B anthracis, is the only licensed human anthrax vaccine available for preexposure prophylaxis.9Advisory Committee on Immunization Practices Use of anthrax vaccine in the United States.MMWR Recomm Rep. 2000; 49: 1-20Google Scholar, 17Drugs and vaccines for biological weapons.Med Lett Drugs Ther. 2001; 43: 87-89PubMed Google Scholar The Food and Drug Administration (FDA) recently approved the release of the vaccine by Bioport's newly renovated facility (Lansing, Mich). Primary vaccination consists of 3 subcutaneous injections of 0.5 mL at 0, 2, and 4 weeks and at 6, 12, and 18 months. Annual boosters are recommended by the manufacturer for continued immunity. Common adverse effects include erythema, tenderness, edema, and induration, although malaise, fever, headache, and myalgia may also occur.9Advisory Committee on Immunization Practices Use of anthrax vaccine in the United States.MMWR Recomm Rep. 2000; 49: 1-20Google Scholar, 18Surveillance for adverse events associated with anthrax vaccination—U.S. Department of Defense, 1998-2000.MMWR Morb Mortal Wkly Rep. 2000; 49: 341-345PubMed Google Scholar Subcutaneous nodules that resolve in weeks to months have also been reported. Local adverse effects are more common in women compared with men. Serious and infrequent adverse events include cellulitis, pneumonia, Guillain-Barré syndrome, sepsis, angioedema, transverse myelitis, and collagen vascular disease. Currently, routine vaccination is limited to military personnel. Penicillin, doxycycline, and ciprofloxacin are FDA approved19Post-exposure anthrax prophylaxis.Conn Med. 2001; 65: 721-722PubMed Google Scholar for treating naturally occurring anthrax. For postexposure prophylaxis (Table 3), oral therapy twice a day with ciprofloxacin, 500 mg, or doxycycline, 100 mg, is recommended. However, if testing indicates susceptibility, the therapy can be switched to penicillin V or amoxicillin, especially for pregnant or lactating women. In the setting of a biocrime, postexposure prophylaxis should be continued for 60 days or more because of the possibility of massive exposure with aerosolized spores. The optimal duration of prophylaxis is unknown. Because of the unusually high concentration of anthrax spores in the recent contaminated letters, the US Department of Health and Human Services has provided 2 other options of an additional 40 days of prophylaxis (a total of 100 days) or a total of 100 days plus 3 doses of the anthrax vaccine over a 4- week period.19Post-exposure anthrax prophylaxis.Conn Med. 2001; 65: 721-722PubMed Google Scholar, 21Centers for Disease Control and Prevention CDC responds: update on options for preventive treatment for persons at risk for inhalational anthrax, December 21, 2001.Available at: www.bt.cdc.gov/agent/anthrax/preventivetreatment12212001.aspGoogle ScholarTable 3Postexposure Prophylaxis for Suspected or Confirmed Exposure to Anthrax*Data from Swartz12 and the Centers for Disease Control and Prevention (CDC) guidelines.20Therapy†Prophylaxis is to be continued for a minimum of 60 days. Recent CDC recommendations include options to continue the prophylaxis for a total of 100 days, with or without 3 doses of anthrax vaccine over a 4-week period.AdultsChildrenCiprofloxacin500 mg orally every 12 h10-15 mg/kg orally every 12 h‡Risks of cartilage damage and staining of teeth by quinolones and tetracyclines, respectively, must be weighed against risk of developing anthrax.§Maximum dose, 1 g/d.Doxycycline‡Risks of cartilage damage and staining of teeth by quinolones and tetracyclines, respectively, must be weighed against risk of developing anthrax.100 mg orally every 12 h≥8 y and >45 kg: 100 mg orally every 12 h; ≥8 y and ≤45 kg: 2.2 mg/kg orally every 12 h; ≤8 y: 2.2 mg/kg orally every 12 hAmoxicillin (if susceptible)500 mg orally every 8 h≥20 kg: 500 mg orally every 12 h; <20 kg: 40 mg/kg per day orally divided every 8 h* Data from Swartz12Swartz MN Recognition and management of anthrax—an update [published correction appears in N Engl J Med. 2002;346:634].N Engl J Med. 2001; 345: 1621-1626Crossref PubMed Scopus (296) Google Scholar and the Centers for Disease Control and Prevention (CDC) guidelines.20Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001.MMWR Morb Mortal Wkly Rep. 2001; 50: 909-919PubMed Google Scholar† Prophylaxis is to be continued for a minimum of 60 days. Recent CDC recommendations include options to continue the prophylaxis for a total of 100 days, with or without 3 doses of anthrax vaccine over a 4-week period.‡ Risks of cartilage damage and staining of teeth by quinolones and tetracyclines, respectively, must be weighed against risk of developing anthrax.§ Maximum dose, 1 g/d. Open table in a new tab For the treatment of inhalation and gastrointestinal anthrax, intravenous administration of ciprofloxacin, 400 mg, or doxycycline, 100 mg, twice a day in addition to 2 other antibiotics with in vitro activity against B anthracis is recommended9Advisory Committee on Immunization Practices Use of anthrax vaccine in the United States.MMWR Recomm Rep. 2000; 49: 1-20Google Scholar, 17Drugs and vaccines for biological weapons.Med Lett Drugs Ther. 2001; 43: 87-89PubMed Google Scholar (Table 4). Since the mortality rate outweighs the risk of adverse effects related to antibiotic therapy, the same regimen is recommended for children and pregnant and breast-feeding women. Because of the persistence of spores after an aerosol exposure, therapy should be continued for a minimum of 60 days. Intravenous therapy may be switched to oral therapy when the patient is clinically improved and stable. An oral regimen of twice-daily ciprofloxacin, 500 mg, or doxycycline, 100 mg, for a total of 60 days is the recommended treatment of cutaneous anthrax in the setting of a bioterrorist attack (Table 5). With clinical improvement of symptoms, amoxicillin can be used to complete therapy. However, cutaneous anthrax with signs of e