Advisory from DHS: Communicating with patients about possible bioterrorism exposures California Department of Health Services Division of Communicable Disease Control
To:             Health Care Providers
From:           California Department of Health Services Division of Communicable Disease Control
Date:           October 17, 2001
Subject:        Alleged Anthrax Exposure - Response Guidelines

• Police and health departments are referring individuals concerned about possible anthrax exposure to see a health care provider.  The purpose of this communication is to provide guidance to those performing medical evaluation and response in these situations.  These guidelines are based on guidance given by the CDC to state health departments, the "Consensus Statement on Anthrax as a Biologic Weapon: Medical and Public Health Management" (JAMA 1999, Vol 281:1735-45,  http://jama.ama-assn.org/) and the current experience of state and local health departments in dealing
  with anthrax threats. 

Protocol for Response to Possible Anthrax Exposures

• People with "powder" incidents should report them to the local police and/or the nearest Division Office of the FBI as soon as possible (phone numbers provided below). The FBI, local law enforcement, local fire departments, and local hazardous materials teams have primary responsibility for determining the credibility of the threat, and, if
  the threat is credible, testing of the substance can be performed at a public health laboratory.

• FBI Division Offices in California-24-hour numbers
  *               Los Angeles             310-477-6565
  *               Sacramento              916-481-9110
  *               San Diego                858-565-1255
  *               San Francisco                     415-553-7400

Specific guidelines for handling suspicious packages or letters and scenes where there is a suspicious powder are given in the CDC Health Alert which is included at the end of this document and can also be found at:
http://www.bt.cdc.gov/DocumentsApp/Anthrax/10122001Handle/10122001Handle.asp

Assessment of Individual Risk of Exposure
*       Much as we do with rabies, it is important to assess the nature of possible exposure to anthrax of any concerned person before deciding on a course of action.  Factors that need to be assessed include credibility of the threat and whether the exposure might result in inhalational anthrax or cutaneous anthrax.  Again, the FBI, local law enforcement, local fire departments, and local hazardous materials teams have primary responsibility for determining the credibility of the threat.  If these threat response personnel believe that the threat is credible, public health should be consulted to help assess whether the exposure might result in inhalational anthrax or cutaneous anthrax.

Credibility
 An exposure to a substance may be higher risk if:
 *       There is a threatening message with the powder or substance
 *       The substance is brown or sandy-brown rather than stark white.  Of note, the positive NBC letter is reported to have had brownish sand-like material in it.
 *       A suspicious letter or package is involved (see the CDC Health Alert for details).

Situations that may be less worrisome for true anthrax or biological agent exposure include:
 *       A white powder is found without a note, where one might expect someone to have spilled sugar, flour, etc.
 *       A white powder comes in an envelope with expected mail that is easy to trace to the sending source.
       

Route of Potential Exposure

 *       Inhalational anthrax generally requires a large dose of invisibly fine powder - particles 1-5 microns in size, the size
necessary to get into the alveoli.  It is technologically very difficult to get anthrax into a form where it can be inhaled.  Re-aerosolization of particles on clothing and on surfaces into particles of this size is nearly impossible.  Thus, visible settled powders and letters or boxes that are opened and contain powders are usually not serious threats for inhalational anthrax. Thus, the immediate risk to people "exposed" in these situations is small.  Inhalational anthrax would be of concern if: a) a person got a face full of fine powder with heavy contamination of eyes, nose and throat; b) there was a real concern of aerosolization based on warning that an air handling system is contaminated or warning that a biological agent was released in a public space.

*       Cutaneous anthrax appears to require lower doses and is the most plausible form of anthrax that could be caused by letters and packages that did not have obvious aerosolizing devices - all one needs is spores rubbed into the skin or cuts in the skin.  Given its characteristic clinical picture and very good prognosis when recognized and treated, potential exposures can readily be managed by  observation and treatment as clinically needed. Risk-based Medical Management of Possible Exposures Low-credibility exposure situations and situations with possible cutaneous exposure

*       If no clear-cut exposure (e.g., patient was in New York, now has cold symptoms and is worried), provide reassurance to the patient about the rarity of infection without known exposures.   We do not recommend collecting a nasal swab or blood for a serologic test to try to confirm that there is no evidence of exposure to anthrax.  We do not recommend prescribing prophylactic antibiotics in these situations.

*       If the only potential exposure to a finding powder on a surface, opening a letter with powder in it),
provide advice on what to look for (red spot -> papule -> vesicle -> black center over several days to a week), reassure them that cutaneous anthrax can be readily diagnosed and easily treated.  We do not recommend collecting a nasal swab or blood for serology in the absence of a skin lesion, nor do we recommend prescribing antibiotic prophylaxis. This situation is analogous to the rabies situation of having a provoked bite from an animal that is highly unlikely to have
rabies - e.g., squirrel that bites finger. 

*      High-credibility exposure situations
The situations described below are ones in which the FBI has already deemed the threat to be credible.  The local health department should be notified immediately.
 *       If the situation suggests real potential for inhalational exposure (e.g., got a face and nose full of powder AND FBI
has deemed the threat to be credible), consider starting prophylactic antibiotics and continuing them until exposure has been ruled out. (This situation is analogous to starting rabies prevention prior to getting a test result back if there is an animal bite to the face from a likely high-risk exposure - where time is of the essence).  If the powder is not available for testing, limited environmental testing of the site where the powder was released (e.g., where the envelope or package was opened) will likely be more sensitive and useful than collecting a nasal swab.  Your local health department may have the capacity to conduct this environmental testing if it is warranted. 
*       If the situation suggests real potential for cutaneous exposure (e.g., direct hand contact with brownish powder AND FBI deems the threat to be credible), provide reassurance and counseling about the signs and symptoms of cutaneous anthrax and wait to start prophylactic antibiotics until culture of the powder is complete.  This is analogous to waiting to start rabies treatment pending testing for plausible rabies exposure - e.g., unprovoked stray cat bite on hand - when you
have time to sort the situation out.  Nasal swab testing is not recommended.
  *       If the person was potentially exposed to anthrax at the America Media Inc. Building in Boca Raton, Florida, the NBC studio (30 Rockefeller Plaza) in New York City, or the Hart Senate Building in Washington, D. C., please call your Local Health Department for specific guidance.

Nasal swabs
        CDC does not recommend the use of nasal swab testing on a routine basis to determine whether a person has been exposed to B. anthracis or as a diagnostic tool that would be relied upon to guide prophylaxis and treatment.   Their use in recent investigations by CDC has been for epidemiologic purposes only, as an adjunct to an environmental investigation where there is a known exposure event, to help determine the extent of exposure. The sensitivity, specificity, and positive/negative predictive value of nasal swab cultures are unknown. In particular, the sensitivity of this method for detecting exposure to B. anthracis spores is unknown.

Serologic testing
        CDC does not recommend the use of serologic testing on a routine basis to determine whether a person has been exposed to B. anthracis or as a diagnostic tool to guide decision about prophylaxis and treatment. As described above for nasal swab testing, the use of serologic tests in recent investigations by CDC has been for epidemiologic purposes only
where there is a known exposure to B. anthracis.  Again, the sensitivity, specificity, and positive/negative predictive value of serologic tests for B. anthracis are unknown.

Prophylactic use of antibiotics
Antibiotic prophylaxis should be limited to those who have a confirmed exposure to B. anthracis or who have had a strongly suspected exposure as described above (FBI assessment that the threat is credible and route of exposure is likely to be inhalational, with gross amounts of powder on the face/nose).  Indiscriminate use of ciprofloxacin and other
antibiotics can contribute to antimicrobial resistance and lessen the effectiveness of these agents against many infections.  Inappropriate stockpiling of ciprofloxacin may threaten the supply of this antibiotic should it be urgently required. If post-exposure prophylaxis is required following a confirmed or strongly suspected exposure to B. anthracis, the following regimens have been recommended by the CDC for use of doxycycline or ciprofloxacin:

        Initial therapy Duration       
Adults, including pregnant women and immuno-compromised persons Ciprofloxacin 500 mg po BID or  Doxycycline 100 mg po BID 60 days (if only suspected but not confirmed exposure, may stop antibiotics if testing of substance rules out exposure to B. anthracis)

Children        Ciprofloxacin 15-20 mg/kg po Q 12 hrs (not to exceed 1 gram/day)  OR Doxycycline  >8 yrs and >45 kg:  100mg po BID      >8 yrs and <=45 kg:  2.2 mg/kg po BID      <=8 yrs:  2.2mg/kg po BID    60 days (if only suspected but not confirmed exposure, may stop antibiotics if testing of substance rules out exposure to B. anthracis)     

 *       If susceptibility testing allows, therapy should be changed to oral amoxicillin for post-exposure prophylaxis to continue therapy out to 60 days.
  *       Although tetracyclines are not recommended during pregnancy, their use may be indicated for life-threatening
illness.  Adverse effects on developing teeth and bones are dose-related, therefore, doxycycline might be used for a short course of therapy (7-14 days) prior to the 6th month of gestation.
*       Use of tetracyclines and fluoroquinolones in children has potential adverse effects.  These risks must be weighed
carefully against the risk for developing life-threatening disease.  If a release of B. anthracis is confirmed, children should be treated initially with ciprofloxacin or doxycycline as prophylaxis, but therapy should be changed to oral amoxicillin 40 mg/kg of body mass per day divided every 8 hours (not to exceed 500 mg TID) as soon as penicillin
susceptibility of the organism has been confirmed. 

Recognition and diagnosis of patients with symptoms compatible with anthrax (adapted from materials from CDC): report patients with illness suspected to be anthrax immediately to your local health department.

Signs and Symptoms of Anthrax Infection:
Inhalational anthrax:  A brief prodrome resembling a viral respiratory illness followed by development of hypoxia and dyspnea, with radiographic evidence of mediastinal widening.  This is the most lethal form of anthrax and results from inspiration of 8,000-40,000 spores of B. anthracis. The incubation of inhalational anthrax among humans is
reported to range between 1 and 7 days but may be as long as 60 days. Host factors, dose of exposure and chemoprophylaxis may play a role. Initial symptoms include sore throat, mild fever, muscle aches and malaise. These may progress to respiratory failure and shock. Meningitis frequently develops. Case-fatality estimates for inhalational anthrax are based on incomplete information regarding exposed populations and infected populations in the few case series and studies that have been published. However, case-fatality is extremely high, even with all possible supportive care including appropriate antibiotics. Records of industrially acquired inhalational anthrax in the United Kingdom before antibiotics were available reveal that 97% of cases were fatal.  With antibiotic treatment the fatality rate is estimated to be at least 75%. Estimates of the impact of the delay in post-exposure prophylaxis or treatment on survival are not known. 

Gastrointestinal anthrax:  Severe abdominal distress followed by fever and signs of septicemia.  This form of anthrax usually follows the consumption of raw or undercooked contaminated meat and usually has an incubation period of 1-7 days. An oropharyngeal and an abdominal form of the disease have also been described. Involvement of the pharynx is
usually characterized by lesions at the base of the tongue, sore throat, dysphagia, fever, and regional lymphadenopathy. Lower bowel inflammation usually causes nausea, loss of appetite, vomiting and fever, followed by abdominal pain, vomiting blood, and bloody diarrhea. The case-fatality rate is estimated to be 25-60%.  The effect of early antibiotic
treatment on that case-fatality rate is not defined.

Cutaneous anthrax:  A skin lesion evolving from a papule, through a vesicular stage, to a depressed black eschar.  This is the most common naturally occurring type of infection (>95%) and usually occurs after skin contact with contaminated meat, wool, hides, or leather from infected animals.  Incubation period ranges from 1-12 days. Skin infection begins as a small papule, progresses to a vesicle in 1-2 days followed by a necrotic ulcer.  The lesion is usually painless, but patients also may have fever, malaise, headache and regional lymphadenopathy.  The case fatality rate for cutaneous anthrax is 20% without, and less than 1% with, antibiotic treatment.

Laboratory diagnosis of anthrax infection in patients with compatible symptoms
 *       Inhalational anthrax: blood gram stain and culture, CSF gram stain and culture (if meningeal signs are
present); chest X-ray
 *       Gastrointestinal anthrax: blood culture
 *       Cutaneous anthrax: vesicular fluid and blood culture

Evaluation of possible anthrax infection for individuals not connected with the AMI incident in Florida should be performed through standard laboratory tests, following the Laboratory Response Network (LRN ) Level A Clinical Guidelines for rule-out and presumptive testing http://www.bt.cdc.gov (follow the link for Resources: Agents/Diseases -
Bacillus anthracis)

a.      Presumptive identification criteria (level A LRN laboratory)
1.      From clinical samples, such as blood, CSF, or skin lesion (vesicular fluid or eschar) material: encapsulated Gram-positive rods
2.      From growth on sheep blood agar: large Gram-positive rods
3.      Non-motile
4.      Non-hemolytic on sheep blood agar

Additional LRN level B laboratory criteria for confirmation of B. anthracis are available through the Los Angeles, Sacramento, San Diego, and San Joaquin County Public Health Laboratories and the state Microbial Diseases Laboratory, and involve:
b.  Confirmatory criteria for identification of B. anthracis (level B LRN laboratory)
 1.      Capsule production (visualization of capsule), and
 2.      Lysis by gamma-phage, or
3.      Direct fluorescent antibody assays (DFA)

Rapid screening assays, such as nucleic acid signatures and antigen detection, which can be performed directly on clinical specimens and environmental samples, are being made available for restricted use in LRN B and C level laboratories.