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Recommendations for Suspected Inhalational Anthrax

October 14, 2001

General Information:

These recommendations are for use for New Hampshire health care providers evaluating patients after exposure to “suspicious” letters or packages. These recommendations are based on the most recent information available from the Centers for Disease Control and Prevention (CDC) and focus on protection of inhalational anthrax given the seriousness of this form of the disease. Health care providers may also find these guidelines useful for evaluating concerns relative to other forms of the disease.

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, the most lethal, form of anthrax results from inspiration of 8,000-40,000 spores of B. anthracis. The incubation of inhalational anthrax among humans is unclear, but it is reported to range between 1 and 7 days possibly ranging up to 42 days, most commonly 2–5 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%. Though estimates of the impact of the delay in postexposure prophylaxis or treatment on survival can only be approximated, it has been suggested that or each day of delay post exposure in initiating prophylaxis the case-fatality rate increases by 5 to 10%. Clinical inhalational anthrax can show both rapidly progressive symptoms and a two-stage progression from mild flu symptoms to severe illness. Mild flu and cold symptoms over 2-3 days duration is unlikely to represent Anthrax infection. The rapidity of symptom progression is dependent on the potential dose of exposure.

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 is considered to have an incubation period of 1-7 days. An oropharyngeal and an abdominal form of the disease have been described in this category. 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 is estimated to be 25-60%, and the effect of early antibiotic treatment on that case-fatality 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, and 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 for cutaneous anthrax is 20% without and 1% with antibiotic treatment.

Table 1: Recommendations for Medical Management of Inhalational Anthrax
Patient risk factor or scenario	Clinical Condition	Treatment	Clinical Laboratory Testing
No suspicious exposure	Asymptomatic or non-specific cold and flu symptoms of over 2 days duration	None	None
Suspicious exposure within the past 2 days with confirmation of negative results in a package or letter	Asymptomatic, or with non-specific cold and flu symptoms of < 2 days duration	None	None
Suspicious exposure within the past 2 days with confirmation that the package is being tested	Asymptomatic	None. Advise patient of symptoms to be alert to and to recontact medical providers if necessary	None
Suspicious exposure within the past 2 days with confirmation that the package is being tested	Non-specific cold and flu symptoms of less than 2 days duration	Use clinical judgment for antibiotic treatment. Advise patient of symptoms to be alert to and to recontact medical providers if necessary	None
Suspicious exposure within the past 2 days without confirmation that the package is being tested	Asymptomatic, or with non-specific cold and flu symptoms of Less than 2 days duration	Use clinical judgment for antibiotic treatment. Advise patient to alert local law enforcement for testing and evaluation of the package or letter.	None
Suspicious exposure within the past 1 week where the letter or package has been evaluated by local law enforcement and is being sent for testing	Non-specific cold and flu symptoms of less than 2 days duration	Presumptive antibiotic treatment, monitor for worsening symptoms	Chest – x-rayBlood smear and culture may be appropriate. Nasal swabs are of no use for clinical diagnosis
Suspicious exposure over a week in the past where the letter or package was not tested or currently is not available for testing	Non-specific cold and flu symptoms of less than 2 days duration	Presumptive antibiotic treatment, monitor for worsening symptoms	Chest – x-rayBlood smear and culture may be appropriate. Nasal swabs are of no use for clinical judgment
Regardless of exposure	Non-specific cold and flu symptoms of greater than 2-3 days duration	None. Unlikely to represent acute anthrax infection.	None.
Regardless of exposure	Severe symptoms requiring hospitalization	Seek Infectious Disease consult	As per Infectious Disease consult

Please Note: Clinical consultation is available by calling the New Hampshire Department of Health and Human Services 24 hours a day 7 days per week through (603) 271-4496 (during business hours) or 271-5300 after hours. The State Public Health Laboratory is available for testing both clinical and other specimens as requested.

Table 2: Post-exposure Antibiotics Recommendations
	Initial therapy	Duration
Adults (including pregnant woman 1,2 and immunocompromised)	Ciprofloxacin 500 mg po BID Or Doxycycline 100 mg po BID	60 days
Children (see cautionary notes below)1,3	Ciprofloxacin 15-20 mg/kg po Q12 hrs 4 Or Doxycycline 5: >8 yrs and >45 kg: 100 mg po BID >8 yrs and = 45 kg: 2.2 mg/kg po BID = 8 yrs: same as >8 yrs and = 45 kg	60 days

1. If susceptibility testing allows, therapy should be changed to oral amoxicillin for post-exposure prophylaxis to continue therapy out to 60 days.
2. Although tetracyclines are not recommended during pregnancy, their use may be indicated for life-threatening illness. Adverse affects 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. Please consult physician after the 6th month of gestation for recommendations.
3. Use of tetracyclines and fluoroquinolones in children has 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 three times daily) as soon as penicillin susceptibility of the organism has been confirmed.
4. Ciprofloxacin dose should not exceed 1 gram/day in children.
5. In 1991, the American Academy of Pediatrics amended their recommendation to allow treatment of young children with tetracyclines for serious infections, such as, Rocky Mountain Spotted Fever, for which doxycycline may be indicated. Doxycycline is preferred for its twice-a-day dosing and low incidence of gastrointestinal side effects.