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ALL SUSPECT CASES OF ANTHRAX MUST BE REPORTED IMMEDIATELY TO THE BUREAU OF COMMUNICABLE DISEASE:
KEY SUMMARY POINTS
Anthrax is a disease caused by Bacillus anthracis (Gram positive bacilli) which can infect most warm-blooded animals, including man. Transmission to humans usually occurs through contact with infected animals or contaminated animal products. Humans become infected by inoculation, inhalation, or ingestion of the bacterium. In humans, naturally-occurring anthrax primarily involves the skin or rarely, the lungs or the gastrointestinal tract. The bacillus produces a resistant spore which could be dispersed as a small particle aerosol. In the event of a biologic terrorist attack, aerosolization is the most likely mode of transmission, and inhalational anthrax would be the predominant form of disease affecting persons exposed to the aerosol.
The spore form of B. anthracis is highly resistant to physical and chemical agents. The organism has been shown to persist for years in factories contaminated during the processing of infected animal products. Soil, animal feed, and to a lesser extent, ground water are the major reservoirs for anthrax.
From the Dermatology Atlas: Cutaneous Anthrax
Would you recognize cutaneous anthrax? From Medscape Dermatology.
Symptoms - Typically biphasic illness
Initial Phase is characterized by flu-like symptoms:
Acute Phase develops after 2-5 days, it may be briefly preceded by 1-2 days of improvement.
Characteristic findings include:
Shock develops rapidly, sometimes accompanied by evidence of hemorrhagic meningitis, and patients usually die within 24 hours of onset of the acute phase. In prior outbreaks, mortality rates approached 90% despite appropriate antibiotic therapy.
The differential diagnosis of acute mediastinitis includes: esophageal perforation; trauma; contiguous spread from a head, neck or thoracic infection; and post-surgical infections after cardiothoracic procedures. Anthrax should be strongly considered in any previously healthy patient with acute mediastinitis.
The key to successful treatment is prompt administration of an antimicrobial at the first suspicion of anthrax. During a biologic emergency, before susceptibility is determined (which may take several days), assume penicillin and tetracycline resistance and treat with ciprofloxacin at 400 mg IV every 12 hours. Penicillin is the antibiotic of choice for treating infections with penicillin-sensitive anthrax.
Treatment for Non-Pregnant Adults:
Rx for Inhalation anthrax (this regimen also recommended for gastrointestinal and meningeal anthrax)
For penicillin resistant anthrax,
administer ciprofloxacin at 400 mg IV every 8 to 12 hours (Alternative quinolone options include: ofloxacin 400 mg IV every 12 hours or levofloxacin 500 mg IV every 24 hours). If the isolate is tetracycline susceptible, doxycycline 200 mg initially, followed by 100mg IV every 12 hours is equally efficacious.
For penicillin susceptible anthrax,
administer Penicillin G IV 80,000 units/kg body weight in the first hour followed by a maintenance dose of 320,000 units/kg body weight/day. The average adult dose is 4 million units every 4 hours; can also be administered as 2 million units every 2 hours. (Amoxicillin 500 mg IV every 8 hours is an alternative regimen, with a dosing schedule that may be easier to administer in the event of a large-scale outbreak.)
Supportive therapy is often required (e.g., volume expanders, vasopressor agents and oxygen). A tracheotomy may be needed if cervical edema compromises the airways.
Universal precautions. Patients do not require isolation rooms.
presents as a "malignant pustule or malignant carbuncle" resulting from introduction of the anthrax bacillus beneath the skin by inoculation or contamination of a pre-existent break in the skin.
Incubation period - ranges from 1-7 days but is commonly 2-5 days
Symptoms - an evolving skin lesion, usually located on the exposed parts of the body (face, neck, arms), with a varying degree of associated edema. The skin lesion typically progresses as follows:
Small, painless, pruritic papule >>> small ring of vesicles that coalesce into a single large vesicle >>> vesicle ruptures to form depressed ulcer >>> 1-3 cm eschar develops in center (7-10 days from onset of lesion) >>> eschar falls off (after 1-2 weeks) leaving a permanent scar.
Systemic symptoms including fever, headache, myalgias, and regional lymphangitis/lymphadenopathy have been described. Lesions on the face and neck may be associated with significant edema and impingement of the trachea from neck swelling can occur. "Malignant edema" describes a syndrome with marked edema, induration and multiple bullae at the site of inoculation associated with generalized toxemia. Septicemia is rare.
Untreated cutaneous anthrax has a case fatality rate up to 20%, but fatalities are rare (< 1%) with effective antibiotic treatment.
occurs after the ingestion of contaminated food, particularly raw or undercooked meat from infected animals. There has never been a case of gastrointestinal anthrax reported in the United States.
Incubation period - ranges from 2-7 days
Symptoms - Two clinical presentations, intestinal and oropharyngeal, have been described.
The symptoms of intestinal anthrax are initially nonspecific and include nausea, vomiting, anorexia and fever. As the disease progresses, abdominal pain, hematemesis and bloody diarrhea develop, occasionally accompanied by ascites. The patient may present with the findings of an acute surgical abdomen. Oropharyngeal anthrax is associated with cervical edema and necrosis. A lesion, resembling a cutaneous anthrax lesion, may be seen in the oral cavity on the posterior wall, the hard palate or the tonsils. Patients typically complain of fever, dysphagia and lymphadenopathy. Toxemia, shock and cyanosis characterize the terminal stages of both forms of the disease. The case fatality rate for gastrointestinal anthrax ranges from 25 to 60%.
Meningitis occurs in less than 5% of cases, and may be a complication of any form of anthrax (inhalational, gastrointestinal or cutaneous). Rarely does it occur without a primary focus. It is usually hemorrhagic.
Incubation period - concurrent with or one to several days after the onset of cutaneous, inhalation or gastrointestinal anthrax.
Symptoms - abrupt onset of meningeal symptoms including nausea, vomiting, myalgia, chills and dizziness. Laboratory findings are notable for a hemorrhagic meningitis.
Encephalomyelitis and cortical hemorrhages have been reported; death occurs in 1-6 days.
Morbidity and Mortality Weekly Report October 2001;50:909-919
Update: Investigation of Bioterrorism-Related Anthrax and Interim Guidelines for Exposure Management and Antimicrobial Therapy
CDC Editorial Note:
Bioterrorism attacks using B. anthracis spores sent through the mail have resulted in 15 anthrax cases and three deaths. The initial anthrax cases occurred among persons with known or suspected contact with opened letters contaminated with B. anthracis spores. Later, investigations identified four confirmed cases and one suspected case among postal workers who had no known contact with contaminated opened letters. This suggests that sealed envelopes contaminated with B. anthracis passing through the postal system may be the source of exposure. The number of contaminated envelopes passing through the postal system is not known. In addition, automated sorting could damage envelopes and release spores into postal environments; other circumstances that could contribute to the contamination of postal facility environments may be identified.
Because these cases are the result of intentional exposures, FBI and other law enforcement authorities are investigating these events as criminal acts and are working to identify and eliminate the source of these exposures. Until that occurs, the possibility of further exposure to B. anthracis and subsequent clinical illness exists. Clinicians and laboratorians should be vigilant for symptoms or laboratory findings that indicate B. anthracis infection, particularly among mail handlers. Information to guide health-care providers and laboratorians is available at http://www.bt.cdc.gov.
Letters containing B. anthracis spores have been sent to persons in NYC and DC. Prompt identification of a threat and institution of appropriate measures may prevent inhalational anthrax. To prevent exposure to B. anthracis and subsequent infection, suspicious letters or packages should be recognized and appropriate protective steps taken.
Characteristics of suspicious packages and letters include inappropriate or unusual labeling, strange return address or no return address, postmarks from a city or state different from the return address, excessive packaging material, and others. If a package appears suspicious, it should not be opened. The package should be handled as little as possible. The room should be vacated and secured promptly and appropriate security or law enforcement agencies promptly notified (see sidebar).
Identification of a patient with anthrax or a confirmed exposure to B. anthracis should prompt an epidemiologic investigation. The highest priority is to identify at-risk persons and initiate appropriate interventions to protect them. The exposure circumstances are the most important factors that direct decisions about prophylaxis. Persons with an exposure or contact with an item or environment known, or suspected to be contaminated with B. anthracisregardless of laboratory tests resultsshould be offered antimicrobial prophylaxis. Exposure or contact, not laboratory test results, is the basis for initiating such treatment. Culture of nasal swabs is used to detect anthrax spores. Nasal swabs can occasionally document exposure, but cannot rule out exposure to B. anthracis. As an adjunct to epidemiologic evaluations, nasal swabs may provide clues to help assess the exposure circumstances. In addition, rapid evaluation of contaminated powder, including particle size and characteristics, may prove useful in assessing the risk for inhalational anthrax.
CDC is working with U.S. Postal Service employees and managers on several strategies to address the risk for anthrax among workers involved in mail handling. These strategies include personal protective equipment for workers handling mail and engineering controls in mail facilities. Clinicians and laboratorians should be vigilant for symptoms or laboratory findings that indicate possible anthrax infection, particularly among workers involved in mail sorting and distribution. Information to guide health-care providers and laboratories is available at http://www.bt.cdc.gov.1
A high index of clinical suspicion and rapid administration of effective antimicrobial therapy is essential for prompt diagnosis and effective treatment of anthrax. Limited clinical experience is available and no controlled trials in humans have been performed to validate current treatment recommendations for inhalational anthrax. Based on studies in nonhuman primates and other animal and in vitro data, ciprofloxacin or doxycycline should be used for initial intravenous therapy until antimicrobial susceptibility results are known (Table 1).
Because of the mortality associated with inhalational anthrax, two or more antimicrobial agents predicted to be effective are recommended; however, controlled studies to support a multiple drug approach are not available. Other agents with in vitro activity suggested for use in conjunction with ciprofloxacin or doxycycline include rifampin, vancomycin, imipenem, chloramphenicol, penicillin and ampicillin, clindamycin, and clarithromycin; but other than for penicillin, limited or no data exist regarding the use of these agents in the treatment of inhalational B. anthracis infection. Cephalosorins and trimethoprim-sulfamethoxazole should not be used for therapy. Regimens being used to treat patients described in this report include ciprofloxacin, rifampin, and vancomycin; and ciprofloxacin, rifampin, and clindamycin.
Penicillin is labelled for use to treat inhalational anthrax. However, preliminary data indicate the presence of constitutive and inducible beta-lactamases in the B. anthracis isolates from Florida, NYC, and DC. Thus, treatment of systemic B. anthracis infection using a penicillin alone (i.e., penicillin G and ampicillin) is not recommended. The B. anthracis genome sequence shows that this organism encodes two beta-lactamases: a penicillinase and a cephalosporinase. Data in the literature also show that some beta-lactamase negative B. anthracis strains for which the penicillin MICs are 0.06 µg/mL increase to 64 µg/mL and become beta-lactamase positive when exposed to semisynthetic penicillins.4 The frequency of this induction event is unknown. Although amoxicillin/clavulanic acid is more active than amoxicillin alone against beta-lactamase, producing strains in vitro, the combination may not be clinically effective for inhalational anthrax where large numbers of organisms are likely to be present.
Toxin-mediated morbidity is a major complication of systemic anthrax. Corticosteroids have been suggested as adjunct therapy for inhalational anthrax associated with extensive edema, respiratory compromise, and meningitis.5
For cutaneous anthrax, ciprofloxacin and doxycycline also are first-line therapy (Table 2). As for inhalational disease, intravenous therapy with a multidrug regimen is recommended for cutaneous anthrax with signs of systemic involvement, for extensive edema, or for lesions on the head and neck. In cutaneous anthrax, antimicrobial treatment may render lesions culture negative in 24 hours, although progression to eschar formation still occurs.5 Some experts recommend that corticosteroids be considered for extensive edema or swelling of the head and neck region associated with cutaneous anthrax. Cutaneous anthrax is typically treated for 7-10 days; however, in this bioterrorism attack, the risk for simultaneous aerosol exposure appears to be high. Although infection may produce an effective immune response, a potential for reactivation of latent infection may exist. Therefore, persons with cutaneous anthrax associated with this attack should be treated for 60 days.
Prophylaxis for inhalational anthrax exposure has been addressed in a previous report1 and indicates the use of either ciprofloxacin or doxycycline as first line agents. High-dose penicillin (e.g., amoxicillin or penicillin VK) may be an option for antimicrobial prophylaxis when ciprofloxacin or doxycycline are contraindicated. The likelihood of beta-lactamase induction events that would increase the penicillin MIC is lower when only small numbers of vegetative cells are present, such as during antimicrobial prophylaxis.
All medications may have undesirable side effects and allergic reactions may result from any medication. Clinicians prescribing these medications should be aware of their side effects and consult an infectious disease specialist as needed. Patients should be urged to inform their health-care provider of any adverse event.
This is the first bioterrorism-related anthrax attack in the United States, and the public health ramifications of this attack continue to evolve. Additional updates and recommendations will be published in MMWR.
Handling of Suspicious Packages or Envelopes
Resources on Bioterrorism & Anthrax
*** Website Resources for Bio-Terrorism
to Physicians on Anthrax
CDC - FAQs about Anthrax
CDC - How to handle Anthrax Threat 10-12-2001
CDC - One Page Fact about Anthrax 10-14-2001
Anthrax JAMA May 12, 1999
Anthrax - NY City Dept. of Health Bio-Threat Website
Anthrax - Background ( CAnthrax BAckground Center for Nonproliferation Studies )
Anthrax Review - Cleveland Clinic December 1999
Review on Anthrax September 9, 1999
NEJM Book Review on Anthrax May 4, 2000