Physician Guidelines for Evaluation of Possible Anthrax Disease

A. General Recommendations:

• Anthrax is not spread from person to person and there is no need to isolate the patient.
  
• Provide support and understanding to prevent panic.
  
• Nasal swabs are not a clinically useful tool for diagnosis of anthrax and are not recommended.

• Postal workers, especially if they work or spend time in (a) a mail distribution center where automated sorting machines are operating or (b) in a New Jersey postal facility.
  
• Employees of media corporations or other high-profile companies/institutions (e.g., government organizations), especially if they routinely handle mail.
  
• Persons reporting a potential high-risk exposure to contaminated powder in the week prior to illness onset (e.g., aerosolization of powder when opening or handling a letter deemed to be a credible threat; criteria for a credible threat include an envelope containing powder that is either (a) addressed to a high-profile person or corporation and/or (b) if the letter contains a written threat).

C. A suspicious case of CUTANEOUS ANTHRAX is defined as:

1. Any person with a highly suspicious skin lesion:
   
   1. An ulcerative lesion with surrounding edema or vesicles,
      AND/OR
      
   2. A blackened eschar forming 3 to 7 days after onset of skin lesion.
2. Any person with a less suspicious skin lesion:
   
   1. An ulcerative or necrotic lesion,
      AND
      
   2. A risk exposure history. At this time, this includes postal workers or delivery persons in regular contact with postal facilities.
3. Any person with a less suspicious skin lesion:
   
   1. An ulcerative or necrotic lesion
      AND
      
   2. Laboratory evidence suggestive of possible B. anthracis infection.
      Examples include:
      1. Gram stain showing positive bacilli from a skin lesion, sterile fluid, or tissue
         
      2. Culture showing encapsulated non-motile, non-hemolytic bacilli from any body fluid or site.

All patients with a skin lesion characteristic of cutaneous anthrax, with or without a known exposure, should have a complete blood count and blood cultures drawn (prior to the administration of antibiotics), and then be treated presumptively with antibiotics and referred to a physician, such as a dermatologist, who is experienced in the management of ulcerative lesions. Ciprofloxacin or doxycycline should be given until susceptibilities are known. If the isolate is susceptible, penicillin or amoxicillin are acceptable alternatives. If laboratory testing is positive for cutaneous anthrax, treatment should continue for at least 14 days (treatment may need to be extended for 60 days if there was a known aerosol exposure).

D. A suspicious case of INHALATIONAL or meningeal anthrax is defined as a patient with:

1. Sepsis or respiratory distress with a widened mediastinum or pleural effusion, especially if hemorrhagic.
   
2. Sepsis with gram-positive rods OR a suspicious Bacillus species identified in blood or cerebrospinal fluid.

To assist in the diagnostic work-up, providers should obtain blood cultures (obtained prior to the administration of antibiotics), a complete blood count and a chest radiograph (to evaluate for mediastinal widening and/or pleural effusions) to diagnose possible early inhalational anthrax infection.

E. Evaluation of Patients:

Nasal swabs are not recommended for determination of anthrax exposure or assessing need for post exposure prophylaxis. Nasal swabs and blood serum tests are used as epidemiological tools to characterize an outbreak when there is a known confirmed biologic agent in an environmental sample. Nasal swabs are not diagnostic tools for anthrax in asymptomatic people, and a positive or negative nasal swab test gives no information on whether a person is infected.

1. Asymptomatic patient WITHOUT known exposure to a confirmed culture-positive
   letter/package or environmental sample:

   Antibiotic prophylaxis is ONLY recommended at this time for postal workers, and persons who visited inside the mail sorting area, such as business visitors, to the Hamilton or West Trenton postal facilities, since September 18, 2001. These guidelines will be updated as more information is available.

2. Asymptomatic patient WITH potential exposure to a confirmed culture-positive letter/package/environment:
   1. Public health authorities should be consulted to determine whether post-exposure prophylaxis has been recommended for the potential exposure. See below section for antibiotic prophylaxis recommendations.
      
   2. Decontaminating the patient, other than by routine washing with soap and water, IS NOT indicated or recommended.

   
   

3. Patients with symptoms/signs compatible with anthrax WITHOUT a known,
   confirmed culture-positive environmental exposure:

   1. Confirm/rule out the diagnosis by obtaining the appropriate laboratory specimens based
      on the clinical form of anthrax that is suspected (inhalation or cutaneous)
      
      1. See guidelines below for appropriate specimen collection for the diagnosis of anthrax infection.
   2. In a suspected case of anthrax, you must notify your state and local health departments immediately. In particular, a high index of suspicion should be maintained for postal workers, and unexplained febrile respiratory illness or unusual or unexplained cutaneous lesions in postal workers should be reported to the state and local health departments.
      
   3. Physicians should also consider other diagnoses and treat accordingly.
      
   4. Based on the clinical assessment, treatment that includes antibiotics effective against anthrax should be included.

   
   

4. Patients with symptoms/signs compatible with anthrax, WITH a known, confirmed culture-positive environmental exposure:
   
   1. Confirm/rule out the diagnosis by obtaining the appropriate laboratory specimens based on the clinical form of anthrax that is suspected (inhalation or cutaneous)
      
      1. See guidelines below for appropriate specimen collection for the diagnosis of anthrax infection.
   2. In a suspected case of anthrax, you must notify your state and local health department immediately.
      
   3. Begin antibiotic therapy that is effective against anthrax

   
   In light of the ongoing outbreak of intentional anthrax associated with contaminated letters, the NJDHSS requests that physicians maintain an increased level of awareness for the occurrence of milder illness that may represent the early warning symptoms of inhalational disease among persons at higher risk for exposure to aerosolized anthrax spores from contaminated letters. NJDHSS requests that all providers seeing patients with a non-specific, febrile flu-like illness obtain a thorough employment history, including whether the patient handles mail, and ask about any recent exposure to suspicious letters or powders.

TESTING FOR ANTHRAX AND USE OF POST EXPOSURE PROPHYLACTIC ANTIBIOTICS IN NEW JERSEY

The recent bioterrorist attack causing an outbreak of anthrax in several states, including New Jersey, has stressed the resources of the public health care system. Part of that stress is a result of some misconceptions on the part of health care providers and the public that must be addressed to eliminate the inappropriate use of tests and antibiotics that could lead to adverse effects among patients. This addresses those issues and is directed at health care providers to assist them in their efforts to manage their patients in a medically sound approach, given our current knowledge.

The NJDHSS discourages the use of nasal swabs for assessing patients concerned about exposure to anthrax as they are not a clinically useful tool. The use of nasal swabs in recent investigations in Florida, NYC, DC, and New Jersey has been for epidemiologic purposes, in order to help determine where suspicious letters were handled in the work area around a confirmed case. The results have been used to guide further investigation and to determine the source of exposure, and to make overall recommendations on prophylaxis for persons involved at the site regardless of individual nasal swab test results.

There is no screening test available for the detection of anthrax infection in an asymptomatic person. The sensitivity and specificity and clinical value of nasal swab testing for an individual patient are unknown. The presence of anthrax spores in the nose only indicates recent exposure and has no predictive value regarding the number of spores inhaled or infectious status of the individual. In addition, nasal swab tests may be reported preliminarily as positive for Bacillus species but may ultimately be negative for B. anthracis when tested in the State Lab.

Serologic tests are available at reference laboratories such as the CDC, but are only performed in symptomatic individuals with a clinical picture consistent with inhalational or cutaneous disease. Serology is not used as a screening or preliminary test in individuals. Preliminary blood tests in symptomatic individuals being evaluated for anthrax, should instead focus on blood cultures (BEFORE antibiotic therapy).

The New Jersey Department of Health and Senior Services (NJDHSS) continues to strongly urge physicians NOT to prescribe post exposure prophylactic antibiotics for persons who are not among the groups recommended for this.
At this time, those recommended for PEP are the following:

1. Postal workers or business visitors to the work areas at the Route 130
   Mail Processing Facility in Hamilton
   
2. Postal workers at the West Trenton Postal Facility in Ewing Township

Although we recognize the heightened concern regarding the threat of bioterrorism with the unfolding events of the past several weeks, antibiotic therapy in asymptomatic individuals should be limited to persons with a known risk exposure.

Prophylactic antibiotics at this time should be limited to persons with a known documented anthrax exposure, or if prophylaxis has been recommended by local, state or federal public health authorities as part of an ongoing investigation at a specific worksite. Clinicians seeing patients who say they may have been exposed to anthrax should assess the individual risk of exposure. If concerned that a high-risk exposure has occurred, please call the NJDHSS at the Emergency Operations Center at 609-538-6030 for medical consultation, BEFORE making treatment recommendations.

Use of prophylactic antibiotics is not without risk. Inappropriate use of antibiotics may result in serious adverse effects (e.g., Clostridium difficile colitis, allergic reactions, interactions with other medications) and will lead to increased antibiotic resistance among microorganisms causing common bacterial infections (e.g., otitis media, pneumonia).

HOW TO REPORT A SUSPICIOUS CASE OF ANTHRAX:

Call the NJDHSS immediately at: 609-588-7500, off hours at 609-392-2020 or the Emergency Operations Center at 609-538-6030

Please have the following information, if available:

• Patient name
  
• Patient contact information
  
• Medical history
  
• Illness onset date
  
• Characteristics and progression of skin lesion
  
• Presence of systemic symptoms
  
• Treatment history
  
• Laboratory and radiologic data
  
• Detailed exposure and employment history

This information will be used to help determine the patient's risk for anthrax infection. When you call to report a case, we will help to determine whether further testing is necessary.

HOW TO ARRANGE FOR TESTING:

A. If it is determined that the patient is a SUSPICIOUS CASE OF CUTANEOUS ANTHRAX the patient should be evaluated by a dermatologist or another physician experienced in the evaluation of ulcerative lesions. If this physician assesses the lesion to be suspicious, the specimens detailed below will be requested. Laboratory testing at the CDC will be prioritized for selected cases only. NJDHSS will arrange transport of the diagnostic specimens from your facility to the NJ Public Health and Environmental Laboratories (PHEL) ONLY AFTER THE CASE HAS BEEN REVIEWED BY NJDHSS. Microbiologic cultures of suspected B. anthracis can be sent to the PHEL.

For SUSPICIOUS CASES OF CUTANEOUS ANTHRAX, recommended specimens include:

1. Culture and gram stain of skin lesion or skin biopsy for testing at your routine microbiology laboratory:
   
   1. Synthetic (non-cotton) swab with non-wooden stick for culture and gram stain of material swabbed from the exudate or the most actively inflamed area of the eschar.
      
   2. Sterile punch biopsy specimen should be sent in sterile saline for culture
      
   3. Send to routine hospital laboratory. If suspicious Bacillus species is identified, contact NJDHSS immediately.
2. Two skin biopsies for PCR, culture and immunohistochemical staining at CDC:
   (If only one biopsy is obtained, it should be placed in formalin).
   
   1. One biopsy specimen in formalin, kept at room temperature, for histopathology and immunohistochemical staining. Paraffin-embedded specimens are acceptable as well.
      
   2. One biopsy specimen in a sterile cup, frozen at -70 C or placed on dry ice, for culture and PCR. If dry ice is unavailable or undeliverable, refrigerate and ship on regular ice.
3. Acute serum for ELISA testing for B. anthracis at CDC (Ideally within 5 days of illness onset)
   
   1. Collect ~5 ml of whole blood in a serum separator tube, refrigerate or keep at room temperature.
      
   2. Spin down as soon as possible.
      
   3. After spinning, separate serum and freeze the tube of serum at -70 C or place on dry ice. If dry ice is unavailable or undeliverable, store frozen and ship on ice.
4. Convalescent serum for ELISA testing for B. anthracis at CDC (14-21 days after acute sera)
   
   1. Collect ~5 ml of whole blood in a serum separator tube, refrigerate or keep at room temperature.
      
   2. Spin down as soon as possible
      
   3. After spinning, separate serum and freeze the tube of serum at -70 C or place on dry ice. If dry ice is unavailable or undeliverable, store frozen and ship on ice.

If the patient is a suspicious case of cutaneous anthrax and is febrile or hospitalized, please also collect:

1. Gram stain and blood culture:
   
2. Send to routine hospital laboratory, if suspicious Bacillus species* is identified, contact immediately
   
3. Whole blood for PCR: (red top tube)

Please be sure to completely and clearly label all specimens with the following information:

1. PATIENTS FIRST AND LAST NAME
   
2. DATE OF BIRTH
   
3. DATE OF COLLECTION OF SPECIMEN
   
4. SITE OF SPECIMEN COLLECTION
   
5. METHOD OF PRESERVATION (formalin, paraffin, frozen)

REMINDER: Specimens will NOT be accepted by PHEL unless clinician has reported and discussed the case with NJDHSS.

B. If it is determined that the patient is A SUSPICIOUS CASE OF INHALATIONAL ANTHRAX, the diagnostic workup should include the tests listed below:

1. Gram stain and routine blood cultures.
   
2. If meningeal signs are present, gram stain and culture of CSF.
   
3. If pleural fluid is present, gram stain and culture of pleural fluid.
   
4. Chest X-ray and/or chest CT to assess for mediastinal and hilar adenopathy.

REMINDER: Specimens will NOT be accepted by PHEL unless the clinician has reported and discussed the case with NJDHSS.

C. If it is determined that the patient is LESS LIKELY TO BE A CASE OF CUTANEOUS ANTHRAX, i.e., the patient has skin lesions in which cutaneous anthrax is on the differential diagnosis, BUT the clinician does not strongly suspect it AND/OR there is low or no risk exposure history AND/OR there is no existing laboratory evidence of Bacillus infection, referral to a dermatologist is recommended. Laboratory testing for cases that are less suspicious for anthrax should be performed using local medical laboratories.

For post-exposure prophylaxis and treatment recommendations see website at http//www.cdc.gov.

Susceptibility results:
Susceptibility results have been performed on the isolates from New Jersey, Florida, New York City and Washington, DC, and all are sensitive to penicillin, amoxicillin, chloramphenicol, tetracycline, clindamycin, ciprofloxacin, and vancomycin. Susceptibilities of the isolate to ceftriaxone and erythromycin were considered intermediate. (Note: Naturally occurring Bacillus anthracis is generally resistant to extended spectrum cephalosporins). The CDC reports that susceptibility data indicates the presence of a cephalosporinase and suggests the presence of a penicillinase as well. Therefore, CDC advises against using penicillin or penicillin-class drugs alone for treatment of anthrax infections. More detailed information on the revised antibiotic recommendations for management of anthrax exposures is available at MMWR site at cdc.gov.

For patients presenting to hospital emergency departments carrying suspicious material with them, the following are recommendations on handling these materials:

• DO NOT PANIC
  
• DO NOT shake or empty the contents of any suspicious package. DO NOT try to clean up powders or fluids
  
• Place the envelope or package in a plastic bag or other container to prevent leakage of contents. If no container is available, cover the package with anything (clothing, garbage can, paper, etc.) and do not remove this cover.
  
• LEAVE the room and CLOSE the door and ask everyone to leave, and prevent others from entering.
  
• WASH hands carefully with soap and water to prevent powder from spreading to face or skin.
  
• CALL local police, notify your building security official and contact DHSS at 609-538-6030.
  
• If possible, list all people who were in the room where the suspicious material was recognized. Provide this list to local police and local health department officials for follow-up investigations.
  
• Remove heavily contaminated clothing and seal in a plastic bag, and give to local police.
  
• The bag should be labeled clearly with the owner's name, contact telephone number and inventory of the bag's contents. The local police will bring the bag to the PHEL in Trenton for testing.
  
• For incidents involving possibly contaminated material, the environment in direct contact with the letter or its contents should be decontaminated with a solution of one part household bleach to 10 parts water, following a crime scene investigation. Personal affects may be decontaminated similarly.
  
• Shower with lots of soap and water as soon as possible. Do not use bleach or disinfectant on your skin.

For more information, please visit the DHSS website at www.state.nj.us/health.