Eye on ID

Anthrax: A disease of herbivores (and a dangerous bioweapon)

Seventeen years ago, on Oct. 2, 2001, an astute ID physician in Florida made a diagnosis of probable anthrax meningitis in a man who was admitted to the ED. This was accomplished with his old school policy approach of personally looking at the cerebrospinal fluid Gram’s stain. That diagnosis and its consequences, in the wake of the 9/11 attacks on the twin towers and the Pentagon, created headlines around the world. It was the first diagnosed case in a series of anthrax bioterrorism attacks that sickened 22 Americans, killing five, after anthrax spores had been mailed to members of congress, the media and others. That astute ID clinician was my co-author, Larry M. Bush, MD, FACP.

by Donald Kaye, MD, MACP

Epidemiology

For the most part, anthrax is a zoonotic infection, and humans are incidental hosts. Human infection is typically linked to infection of herbivores (eg, cattle, horses, sheep) from the soil where they graze. Spores of Bacillus anthracis are prevalent throughout the world and, depending on environmental conditions, can survive in soil for months to years. Animal vaccination has greatly reduced but not eliminated the number of herbivores that become infected. In North America, animal cases are only sporadically reported.

Infection is transmitted to humans after exposure to infected animals or animal products that are contaminated with the dormant spores, most commonly wool, hair, hides, meat, bones and bone meal or by contaminated foodstuffs. Human infection occurs by three major routes: cutaneous, inhalational and gastrointestinal. Rare cases of soft tissue and systemic infection have been associated with the injection, snorting and smoking of heroin possibly contaminated with anthrax spores, as well as playing or handling drums made from goat hides imported from countries where anthrax is endemic.

Larry M. Bush
Donald Kaye

Unreliable reporting makes it difficult to accurately estimate the true incidence of human anthrax, which in 1958 was reported to be between 20,000 and 100,000 cases worldwide annually. Currently, according to WHO, the yearly global incidence of human anthrax is between 2,000 to 20,000 cases.

In the United States, cases are rare and are almost always cutaneous. Before the 2001 anthrax attacks, which used the U.S. Postal Service to deliver the anthrax, there had only been 18 cases of inhalational anthrax reported in the U.S. since 1900 — all because of occupational exposures, usually with a contaminated animal product — and none after 1976.

Pathogenesis and virulence

Local and systemic disease manifestations result from anthrax toxin-induced cell damage and death. Spore germination requires a nutrient-rich environment, such as human or animal tissues and blood, to convert to the vegetative (or proliferative) form. The exuberant virulence of B. anthracis depends on its antiphagocytic (polypeptide) capsule, three toxin factors — protective antigen (PA), lethal factor (LF) and edema factor — and its capability for rapid replication, resulting in a large bacterial burden.

Clinical manifestations

Cutaneous anthrax

Referred to as “malignant pustule,” cutaneous anthrax is the most common form of infection, accounting for more than 95% of reported cases. Cases in the U.S. have fallen from about 200 per year in the early 1900s to a current incidence of almost none. Although infection can occur with intact skin, most times lesions develop in 1 to 10 days following exposure to abraded skin. Within 48 hours, toxins promote the formation of a macule, which evolves to a papule, and then to an ulcer that may be surrounded by fluid-filled, bacillus-containing vesicles. The lesion is often pruritic but is not painful and is frequently surrounded by an area of induration or edema, or both. The ulcer becomes a black eschar that generally falls off in 1 to 2 weeks. Associated regional lymphadenitis may occur but systemic signs of illness are rare unless there is secondary seeding of the bloodstream. Antimicrobial treatment is curative but mortality rates are approximately 20% without therapy. Staphylococcal furuncles, cat scratch disease, plague, tularemia, scrub typhus, spider bite, and ecthyma gangrenosum must be considered in the differential diagnosis.

Injection anthrax

Injection anthrax is a rare cutaneous infection that was first described in the early 2000s in heroin users in Northern European countries. Most times, the disease is more severe and extensive than classic cutaneous infection, with massive edema, deeper abscesses, necrotizing fasciitis and an increased risk for systemic dissemination. The diagnosis is easily confused with similar complex soft tissue infections involving other pathogens that are frequently encountered in injection drug users.

Inhalation anthrax

Inhalational anthrax is so extremely rare that even one case should suggest the possibility of bioterrorism, as it did in 2001 in Florida. When dispersed in the air as 1- to 5-µm particles, the endospores pose a risk over large geographic distances. Before the 2001 anthrax attacks, it was estimated that the median dose of spores necessary to be lethal was in the range of 2,500 to 55,000. However, based on mathematical models studied following the attacks when up to 10,000 people may have been exposed, researchers found that many fewer spores were sufficient to infect and kill humans. The most extensive experience with inhalational anthrax followed an unintentional release of aerosolized anthrax spores from a military research facility in Sverdlovsk, Russia, in 1979, resulting in 79 diagnosed patients, 68 of whom died. Human cases of anthrax occurred as far as 4 km from the site, and cases in animals occurred as far away as 50 km.

Source: CDC

Bacillus anthracis in cerebrospinal fluid.

Inhaled pathogenic spores are deposited in the alveolar spaces, where they are phagocytized by pulmonary macrophages. Spores that are not destroyed by these cells are transported to mediastinal and pulmonary hilar lymph nodes, where they may remain dormant for up to several weeks. What stimuli trigger their germination is unknown, but once in their vegetative state, the bacteria rapidly multiply and produce toxins that are ultimately responsible for tissue damage (hemorrhagic mediastinitis) and massive septicemia. Following an incubation period, which may range from a few days to a few months, the initial symptoms of inhalational anthrax are vague and nonspecific, resembling an influenza-like illness. The rapid onset of a septic syndrome and the development of multisystem organ failure generally follow if appropriate treatment is not promptly initiated. The immediate suspicion and diagnosis of the index case of inhalational anthrax in the bioterrorism attacks in 2001 led to the early recognition and treatment of subsequent cases and the lowest mortality rate (45%) compared with historical statistics, which show that 89% of previously diagnosed U.S. patients after 1900 and 86% of Sverdlovsk patients died.

Gastrointestinal anthrax

The rare documented cases of gastrointestinal anthrax are believed to have resulted from the ingestion of poorly cooked animal meat contaminated with anthrax spores, although infection probably also occurs by eating vegetative organisms. The oropharyngeal clinical subtype is characterized by ulcerations in the mouth, pharynx and esophagus, leading to sepsis, and the intestinal type involves predominantly the ileum and cecum, causing abdominal pain, diarrhea — which may become bloody — and/or ascites, and then progresses to septicemia. The high case fatality rate (25% to 60%) is presumably owed to late diagnosis.

Central nervous system anthrax

Any route of infection by B. anthracis may result in hemorrhagic meningitis or meningoencephalitis, which carries a fatality rate of more than 95%. Most cases of central nervous system (CNS) involvement are secondary to inhalational anthrax and occur in about 50% of cases of that type. Primary CNS infection has rarely been reported. The symptoms of anthrax-related meningitis are similar to those caused by other organisms; the diagnosis depends on cerebrospinal fluid analysis and isolation of the anthrax bacteria.

Diagnosis

The diagnosis of anthrax relies on the identification of the causative organism in blood, tissue or fluid samples, which are ideally collected for culture before the administration of antibiotics. The rapid and progressive nature of infection, as well as its potential implication of bioterrorism, makes it imperative to consider anthrax being the pathogen in the correct clinical setting based on preliminary microbiologic features. These include its Gram’s stain and encapsulation qualities, rapid growth on blood agar in the absence of hemolysis, colony morphology (“curly hair” or “medusa head-like”), the identification of spores from culture plates, its sensitivity to penicillin, and biochemical testing. Suspicious isolates should be sent for confirmatory testing to one of the government’s Laboratory Response Network facilities. Acute and convalescent serum samples should be collected for serologic assays. Other available tests include an enzyme-linked immunosorbent assay for antibodies to PA and another for detecting LF toxin in acute-phase serum. Stool, rectal and oropharyngeal swab specimens and ascitic fluid (if present) should be submitted for culture and PCR testing if gastrointestinal disease is suspected. Because of the concern and possibility of genetic engineering, all B. anthracis isolates should undergo full antimicrobial susceptibility testing.

Mediastinal widening on chest radiograph or CT scan caused by enlarged lymph nodes due to hemorrhagic lymphadenitis has been described as pathognomonic of inhalation anthrax. When present, pulmonary infiltrates and consolidation relate to edema fluid rather than pneumonia because anthrax is not considered to be an airspace disease. Serosanguinous and hemorrhagic pleural effusions are common.

Treatment, PEP and prevention

Prompt diagnosis and expeditiously administered adequate antimicrobial agents for anthrax infection, together with supportive medical care, have been proven to favorably affect survivability. Nonsevere cutaneous disease without systemic manifestations can be treated with 7 to 10 days of oral amoxicillin. However, if there is suspicion of an intentional release of anthrax, therapy should be the same as for inhalational disease because beta-lactam resistance is a concern. Initial IV therapy consists of a combination of ciprofloxacin, levofloxacin, doxycycline or moxifloxacin, along with a carbapenem, vancomycin or penicillin for susceptible strains, plus a protein synthesis inhibitor, such as linezolid, clindamycin or chloramphenicol, or rifampin for at least 2 weeks or until the patient is stable. The superior CNS penetration of meropenem makes it the preferred treatment for suspected meningitis cases. Because ungerminated spores may persist in the lungs, therapy is continued to prevent relapse using a single oral medication — either a fluoroquinolone or doxycycline — for 60 days. The toxin-neutralizing human monoclonal antibodies raxibacumab and obiltoxaximab bind PA and, when given early and combined with antibacterial therapy, have proven beneficial, as has anthrax immune globulin. The addition of corticosteroids may be considered for anthrax meningitis or when severe mediastinal edema is present.

Post-exposure prophylaxis (PEP) antibiotics against anthrax, together with a three-dose series of anthrax vaccine adsorbed, should be initiated promptly following the actual or potential inhalation of aerosolized B. anthracis spores. The decision to initiate therapy should be based on the likelihood of exposure and not on laboratory testing. Ciprofloxacin, levofloxacin and doxycycline have been approved for use as anthrax PEP and are prescribed for 60 days. Amoxicillin is an alternative in pregnant women and children when the strain involved is known to be sensitive to penicillin. PEP is not indicated for household or work contacts or health care workers who are exposed to patients with anthrax, nor is it given to prevent cutaneous anthrax. Standard hospital universal precautions in a regular hospital room also apply to an anthrax-infected patient.

Pre-exposure vaccination is licensed for use in adults and is designated for military personnel; certain laboratory workers; veterinarians; persons who handle potentially infected animal products; and first responders in the event of an anthrax attack. It is administered as a primary series of two injections, followed by three booster injections. The CDC recommends annual booster injections for ongoing protection.

Lessons learned from the 2001 attacks

“Biowarfare” is defined as the manufacture or intentional use by a political regime of a modified biological agent with the goal of causing massive loss of human life in the context of a declared war. The goal of “bioterrorism,” whether overt or covert, has less to do with causing mortal harm than it is to disrupt our way of life and make us clearly aware of our vulnerability. Because it poses a risk to national security, anthrax has long been on the top of the CDC’s “Category A” list of putative biologic threats. The economic, social and political consequences resulting from 2001 acts of bioterrorism were enormous. Positive lessons were learned from the attack, including the medical community’s ability to recognize bioterrorist-related disease; the laboratory’s ability to identify the pathogen; the deployment of the National Pharmaceutical Stockpile, which was created in 1999 to ensure the country’s readiness against potential agents of bioterrorism; and the willingness of many to accept risk and responsibility. Conversely, the nonuniform and varied preparedness of communities; poor communication from the top down; and outdated and incorrect scientific knowledge (eg, the relative ease of passage of anthrax spores through unopened envelopes and the much smaller quantity of spores necessary to cause disease) were some of the lessons that did not go so well. In addition, the nature of the investigation of the attacks (epidemiological vs. criminal) and who had jurisdiction (local, state or federal officials) were unclear.

Before the 2001 anthrax attacks, and to a greater extent since then, the CDC has relied on syndromic surveillance systems to enhance early detection of illnesses caused by biologic agents that could be used in a bioterrorism attack. This program was not successful in 2001, with four individuals in New York City having been seen and treated for skin lesions that later were established to be cutaneous anthrax following the diagnosis of the index case of anthrax in Florida. Because of the rapid diagnosis and notification of local and federal authorities of the concern for bioterrorism, more than 10,000 presumably exposed persons were given PEP, which has since been statistically estimated to have saved many lives. In considering whether we are now better prepared, it is important to remember that identification of the index case was made possible through the on-site and bedside ability of an individual clinician (in this case an ID specialist) and laboratory personnel to recognize a potential case of bioterrorism. To paraphrase Louis Pasteur’s quote, luck is where the road of opportunity crosses the road of preparation.

Disclosures: Bush and Kaye report no relevant financial disclosures.

Seventeen years ago, on Oct. 2, 2001, an astute ID physician in Florida made a diagnosis of probable anthrax meningitis in a man who was admitted to the ED. This was accomplished with his old school policy approach of personally looking at the cerebrospinal fluid Gram’s stain. That diagnosis and its consequences, in the wake of the 9/11 attacks on the twin towers and the Pentagon, created headlines around the world. It was the first diagnosed case in a series of anthrax bioterrorism attacks that sickened 22 Americans, killing five, after anthrax spores had been mailed to members of congress, the media and others. That astute ID clinician was my co-author, Larry M. Bush, MD, FACP.

by Donald Kaye, MD, MACP

Epidemiology

For the most part, anthrax is a zoonotic infection, and humans are incidental hosts. Human infection is typically linked to infection of herbivores (eg, cattle, horses, sheep) from the soil where they graze. Spores of Bacillus anthracis are prevalent throughout the world and, depending on environmental conditions, can survive in soil for months to years. Animal vaccination has greatly reduced but not eliminated the number of herbivores that become infected. In North America, animal cases are only sporadically reported.

Infection is transmitted to humans after exposure to infected animals or animal products that are contaminated with the dormant spores, most commonly wool, hair, hides, meat, bones and bone meal or by contaminated foodstuffs. Human infection occurs by three major routes: cutaneous, inhalational and gastrointestinal. Rare cases of soft tissue and systemic infection have been associated with the injection, snorting and smoking of heroin possibly contaminated with anthrax spores, as well as playing or handling drums made from goat hides imported from countries where anthrax is endemic.

Larry M. Bush
Donald Kaye

Unreliable reporting makes it difficult to accurately estimate the true incidence of human anthrax, which in 1958 was reported to be between 20,000 and 100,000 cases worldwide annually. Currently, according to WHO, the yearly global incidence of human anthrax is between 2,000 to 20,000 cases.

In the United States, cases are rare and are almost always cutaneous. Before the 2001 anthrax attacks, which used the U.S. Postal Service to deliver the anthrax, there had only been 18 cases of inhalational anthrax reported in the U.S. since 1900 — all because of occupational exposures, usually with a contaminated animal product — and none after 1976.

PAGE BREAK

Pathogenesis and virulence

Local and systemic disease manifestations result from anthrax toxin-induced cell damage and death. Spore germination requires a nutrient-rich environment, such as human or animal tissues and blood, to convert to the vegetative (or proliferative) form. The exuberant virulence of B. anthracis depends on its antiphagocytic (polypeptide) capsule, three toxin factors — protective antigen (PA), lethal factor (LF) and edema factor — and its capability for rapid replication, resulting in a large bacterial burden.

Clinical manifestations

Cutaneous anthrax

Referred to as “malignant pustule,” cutaneous anthrax is the most common form of infection, accounting for more than 95% of reported cases. Cases in the U.S. have fallen from about 200 per year in the early 1900s to a current incidence of almost none. Although infection can occur with intact skin, most times lesions develop in 1 to 10 days following exposure to abraded skin. Within 48 hours, toxins promote the formation of a macule, which evolves to a papule, and then to an ulcer that may be surrounded by fluid-filled, bacillus-containing vesicles. The lesion is often pruritic but is not painful and is frequently surrounded by an area of induration or edema, or both. The ulcer becomes a black eschar that generally falls off in 1 to 2 weeks. Associated regional lymphadenitis may occur but systemic signs of illness are rare unless there is secondary seeding of the bloodstream. Antimicrobial treatment is curative but mortality rates are approximately 20% without therapy. Staphylococcal furuncles, cat scratch disease, plague, tularemia, scrub typhus, spider bite, and ecthyma gangrenosum must be considered in the differential diagnosis.

Injection anthrax

Injection anthrax is a rare cutaneous infection that was first described in the early 2000s in heroin users in Northern European countries. Most times, the disease is more severe and extensive than classic cutaneous infection, with massive edema, deeper abscesses, necrotizing fasciitis and an increased risk for systemic dissemination. The diagnosis is easily confused with similar complex soft tissue infections involving other pathogens that are frequently encountered in injection drug users.

Inhalation anthrax

Inhalational anthrax is so extremely rare that even one case should suggest the possibility of bioterrorism, as it did in 2001 in Florida. When dispersed in the air as 1- to 5-µm particles, the endospores pose a risk over large geographic distances. Before the 2001 anthrax attacks, it was estimated that the median dose of spores necessary to be lethal was in the range of 2,500 to 55,000. However, based on mathematical models studied following the attacks when up to 10,000 people may have been exposed, researchers found that many fewer spores were sufficient to infect and kill humans. The most extensive experience with inhalational anthrax followed an unintentional release of aerosolized anthrax spores from a military research facility in Sverdlovsk, Russia, in 1979, resulting in 79 diagnosed patients, 68 of whom died. Human cases of anthrax occurred as far as 4 km from the site, and cases in animals occurred as far away as 50 km.

PAGE BREAK

Source: CDC

Bacillus anthracis in cerebrospinal fluid.

Inhaled pathogenic spores are deposited in the alveolar spaces, where they are phagocytized by pulmonary macrophages. Spores that are not destroyed by these cells are transported to mediastinal and pulmonary hilar lymph nodes, where they may remain dormant for up to several weeks. What stimuli trigger their germination is unknown, but once in their vegetative state, the bacteria rapidly multiply and produce toxins that are ultimately responsible for tissue damage (hemorrhagic mediastinitis) and massive septicemia. Following an incubation period, which may range from a few days to a few months, the initial symptoms of inhalational anthrax are vague and nonspecific, resembling an influenza-like illness. The rapid onset of a septic syndrome and the development of multisystem organ failure generally follow if appropriate treatment is not promptly initiated. The immediate suspicion and diagnosis of the index case of inhalational anthrax in the bioterrorism attacks in 2001 led to the early recognition and treatment of subsequent cases and the lowest mortality rate (45%) compared with historical statistics, which show that 89% of previously diagnosed U.S. patients after 1900 and 86% of Sverdlovsk patients died.

Gastrointestinal anthrax

The rare documented cases of gastrointestinal anthrax are believed to have resulted from the ingestion of poorly cooked animal meat contaminated with anthrax spores, although infection probably also occurs by eating vegetative organisms. The oropharyngeal clinical subtype is characterized by ulcerations in the mouth, pharynx and esophagus, leading to sepsis, and the intestinal type involves predominantly the ileum and cecum, causing abdominal pain, diarrhea — which may become bloody — and/or ascites, and then progresses to septicemia. The high case fatality rate (25% to 60%) is presumably owed to late diagnosis.

Central nervous system anthrax

Any route of infection by B. anthracis may result in hemorrhagic meningitis or meningoencephalitis, which carries a fatality rate of more than 95%. Most cases of central nervous system (CNS) involvement are secondary to inhalational anthrax and occur in about 50% of cases of that type. Primary CNS infection has rarely been reported. The symptoms of anthrax-related meningitis are similar to those caused by other organisms; the diagnosis depends on cerebrospinal fluid analysis and isolation of the anthrax bacteria.

Diagnosis

The diagnosis of anthrax relies on the identification of the causative organism in blood, tissue or fluid samples, which are ideally collected for culture before the administration of antibiotics. The rapid and progressive nature of infection, as well as its potential implication of bioterrorism, makes it imperative to consider anthrax being the pathogen in the correct clinical setting based on preliminary microbiologic features. These include its Gram’s stain and encapsulation qualities, rapid growth on blood agar in the absence of hemolysis, colony morphology (“curly hair” or “medusa head-like”), the identification of spores from culture plates, its sensitivity to penicillin, and biochemical testing. Suspicious isolates should be sent for confirmatory testing to one of the government’s Laboratory Response Network facilities. Acute and convalescent serum samples should be collected for serologic assays. Other available tests include an enzyme-linked immunosorbent assay for antibodies to PA and another for detecting LF toxin in acute-phase serum. Stool, rectal and oropharyngeal swab specimens and ascitic fluid (if present) should be submitted for culture and PCR testing if gastrointestinal disease is suspected. Because of the concern and possibility of genetic engineering, all B. anthracis isolates should undergo full antimicrobial susceptibility testing.

PAGE BREAK

Mediastinal widening on chest radiograph or CT scan caused by enlarged lymph nodes due to hemorrhagic lymphadenitis has been described as pathognomonic of inhalation anthrax. When present, pulmonary infiltrates and consolidation relate to edema fluid rather than pneumonia because anthrax is not considered to be an airspace disease. Serosanguinous and hemorrhagic pleural effusions are common.

Treatment, PEP and prevention

Prompt diagnosis and expeditiously administered adequate antimicrobial agents for anthrax infection, together with supportive medical care, have been proven to favorably affect survivability. Nonsevere cutaneous disease without systemic manifestations can be treated with 7 to 10 days of oral amoxicillin. However, if there is suspicion of an intentional release of anthrax, therapy should be the same as for inhalational disease because beta-lactam resistance is a concern. Initial IV therapy consists of a combination of ciprofloxacin, levofloxacin, doxycycline or moxifloxacin, along with a carbapenem, vancomycin or penicillin for susceptible strains, plus a protein synthesis inhibitor, such as linezolid, clindamycin or chloramphenicol, or rifampin for at least 2 weeks or until the patient is stable. The superior CNS penetration of meropenem makes it the preferred treatment for suspected meningitis cases. Because ungerminated spores may persist in the lungs, therapy is continued to prevent relapse using a single oral medication — either a fluoroquinolone or doxycycline — for 60 days. The toxin-neutralizing human monoclonal antibodies raxibacumab and obiltoxaximab bind PA and, when given early and combined with antibacterial therapy, have proven beneficial, as has anthrax immune globulin. The addition of corticosteroids may be considered for anthrax meningitis or when severe mediastinal edema is present.

Post-exposure prophylaxis (PEP) antibiotics against anthrax, together with a three-dose series of anthrax vaccine adsorbed, should be initiated promptly following the actual or potential inhalation of aerosolized B. anthracis spores. The decision to initiate therapy should be based on the likelihood of exposure and not on laboratory testing. Ciprofloxacin, levofloxacin and doxycycline have been approved for use as anthrax PEP and are prescribed for 60 days. Amoxicillin is an alternative in pregnant women and children when the strain involved is known to be sensitive to penicillin. PEP is not indicated for household or work contacts or health care workers who are exposed to patients with anthrax, nor is it given to prevent cutaneous anthrax. Standard hospital universal precautions in a regular hospital room also apply to an anthrax-infected patient.

Pre-exposure vaccination is licensed for use in adults and is designated for military personnel; certain laboratory workers; veterinarians; persons who handle potentially infected animal products; and first responders in the event of an anthrax attack. It is administered as a primary series of two injections, followed by three booster injections. The CDC recommends annual booster injections for ongoing protection.

PAGE BREAK

Lessons learned from the 2001 attacks

“Biowarfare” is defined as the manufacture or intentional use by a political regime of a modified biological agent with the goal of causing massive loss of human life in the context of a declared war. The goal of “bioterrorism,” whether overt or covert, has less to do with causing mortal harm than it is to disrupt our way of life and make us clearly aware of our vulnerability. Because it poses a risk to national security, anthrax has long been on the top of the CDC’s “Category A” list of putative biologic threats. The economic, social and political consequences resulting from 2001 acts of bioterrorism were enormous. Positive lessons were learned from the attack, including the medical community’s ability to recognize bioterrorist-related disease; the laboratory’s ability to identify the pathogen; the deployment of the National Pharmaceutical Stockpile, which was created in 1999 to ensure the country’s readiness against potential agents of bioterrorism; and the willingness of many to accept risk and responsibility. Conversely, the nonuniform and varied preparedness of communities; poor communication from the top down; and outdated and incorrect scientific knowledge (eg, the relative ease of passage of anthrax spores through unopened envelopes and the much smaller quantity of spores necessary to cause disease) were some of the lessons that did not go so well. In addition, the nature of the investigation of the attacks (epidemiological vs. criminal) and who had jurisdiction (local, state or federal officials) were unclear.

Before the 2001 anthrax attacks, and to a greater extent since then, the CDC has relied on syndromic surveillance systems to enhance early detection of illnesses caused by biologic agents that could be used in a bioterrorism attack. This program was not successful in 2001, with four individuals in New York City having been seen and treated for skin lesions that later were established to be cutaneous anthrax following the diagnosis of the index case of anthrax in Florida. Because of the rapid diagnosis and notification of local and federal authorities of the concern for bioterrorism, more than 10,000 presumably exposed persons were given PEP, which has since been statistically estimated to have saved many lives. In considering whether we are now better prepared, it is important to remember that identification of the index case was made possible through the on-site and bedside ability of an individual clinician (in this case an ID specialist) and laboratory personnel to recognize a potential case of bioterrorism. To paraphrase Louis Pasteur’s quote, luck is where the road of opportunity crosses the road of preparation.

Disclosures: Bush and Kaye report no relevant financial disclosures.