Suspected Anthrax Exposure

Purpose

The purpose of these policy guidelines is to recommend procedures for handling potential biological threats of Anthrax exposure.

Description of AgentlSyndrome

Anthrax is an infection caused by a gram positive spore-forming bacterium, Bacillus anthracis. There are three main forms of the disease depending on the route of exposure: pulmonary, cutaneous or gastrointestinal.

The organism forms spores when exposed to ambient air. Spores can survive for years. Spores germinate when they enter an environment rich in amino acids, nucleosides and glucose such as that found in blood or tissues of an animal or human. The bacterium then multiplies and in conjunction with toxins causes disease.

Transmission

Humans become infected through skin contact (portal of entry is cut or abrasion), ingestion or inhalation of the organism/spores from infected animals (most frequently sheep, goats or cattle) or animal products such as hides or hair, or intentional acts such as bioterrorism. Person-to-person transmissions of inhalation disease DOES NOT occur. Direct exposure to fluids from skin lesions may result in secondary cutaneous infection.

Incubation

Varies with type — see Signs and Symptoms

Signs and Symptoms

1. Cutaneous (skin) Anthrax

a) 1-7 days incubation period after direct contact with organism.

b) Local skin involvement, often seen on arms, hands, face or neck.

• Small vesicles surround the papule or a larger vesicle develops within 1-2 more days which is filled with serosanquinous fluid. Non-pitting gelatinous edema surrounds the lesion.

• Vesicle enlarges, forms a painless ulcer covered by a characteristic black eschar (1-3 cm in diameter).

• Massive edema may be present at the site.

• The eschar dries and falls off in 1-2 weeks.

• Mortality can be 20% without antibiotics and 1% with antibiotic therapy.

2. Gastrointestinal

• 2-5 day incubation period after the ingestion of undercooked contaminated meat.

• Nausea, vomiting, fever, abdominal pain.

• Progresses to severe bloody diarrhea and bloody emesis.

• Mortality may be greater than 50%.

3. Inhalation
• 1-6 day incubation period after germination (note: spores can survive up to 60 days
in the nasopharynx). Biphasic illness starting with nonspecific influenza like illness:
mild fever, malaise, myalgia, non-productive cough and some chest or abdominal pain.
• Progresses abruptly to second phase in 2-3 days includes fever, acute dyspnea, diaphoresis, cyanosis,

respiratory failure and shock.
• Meningitis is a potential complication of inhalation anthrax.
• Mortality rate high with no or delayed treatment.

Diagnosis

No rapid screening test is available to diagnose anthrax

I. Testing of Symptomatic Patients for Anthrax

Suspected anthrax cases should be reported immediately to the local health department. The health department will provide assistance with testing decisions and facilitate communication with ODH and CDC. Antigen detection may be available through a reference laboratory or CDC. Nasal swabs are not currently recommended for diagnosis of symptomatic patients.

II. Testing of Asymptomatic Patients for Anthrax

There is no reliable clinical test for detection of anthrax exposure in asymptomatic individuals. The use of nasal cultures (swabs) is NOT recommended and should be discouraged. Nasal swabs will ONLY be done under the direction of government agencies. A negative nasal culture does not rule out anthrax infection or exposure. The hospital cannot process nasal swabs to rule out anthrax.

III. Testing Suspicious Items/Substances

The local law enforcement authorities and local health departments handle all suspicious substances/items. The ODH laboratory processes all suspicious substances/items. The hospital will not test or accept these items in their laboratory.

	DIAGNOSTIC STUDIES	CULTURES*
INHALATION ANTHRAX	chest X-ray and/or chest CT peripheral blood smear gram stain of CSF** gram stain pleural/ascitic fluid	blood CSF** pleural/ascitic fluid
CUTANEOUS ANTHRAX	gram stain of skin lesion gram stain of skin biopsy peripheral blood smear	blood vesicular fluid sterile punch biopsy
GASTROINTESTINAL ANTHRAX		blood stool

* sputum cultures and gram stains unlikely to be diagnostic

** if meningeal signs present

1. Cutaneous

Distinguishing cutaneous anthrax from other skin lesions includes several other etiologies in the differential.

Other etiology	Feature different than Anthrax	Anthrax Symptoms
Staph furuncle ecthyma	· Usually painful · Usually without edema	· Painless · With edema
Ecthyma gangrenosum	· Usually in patients with neutropenia	· Can be in a healthy host
Orf (Virus)	· Gelatinous edema absent · Scab forms but no large eschar	· With gelatinous edema present
Brown recluse spider bite	· Painful and incipient necrosis	· Painless

2. Inhalation:

The following table lists clinical features to help distinguish Inhalation Anthrax from other influenza like illnesses.

Symptoms and signs of inhalation anthrax, laboratory-confirmed influenza, and influenza-like illness (ILl) from other causes

Symptoms/Signs	Inhalation Anthrax (n=1O)	Lab-confirmed influenza	ILl from other causes
elevated temperature	70%	68%-77%	40%-73%
fever or chills	100%	83%-90%	75%-89%
fatigue/malaise	100%	75%-94%	62%-94%
cough (minimal or nonproductive)	90%	84%-93%	72%-80%
shortness of breath	80%	6%	6%
chest discomfort or pleuritic chest pain	60%	35%	23%
headache	50%	84%-91%	74%-89%
myalgias	50%	67%-94%	73%-94%
sore throat	20%	64%-84%	64%-84%
rhinorrhea	10%	79%	68%
nausea or vomiting	80%	12%	12%
abdominal pain	30%	22%	22%

Treatment

1. Cutaneous Anthrax

Mild cases of cutaneous anthrax in adults, oral treatment with ciprofloxacin (500 mg every 12 hours) is

recommended.

If the strain is susceptible, oral doxycyline (100 mg every 12 hours) or amoxicillin (500 mg every 8 hours) is

a suitable alternative. Treatment should continue for 60 days in the context of bioterrorism, as opposed to

7 to 10 days for naturally acquired disease.

Severe cutaneous anthrax is treated with the same drugs and dosages as inhalational anthrax.

2. Inhalation Anthrax

Recommendations for Antimicrobial Therapy of Clinical Inhalational Anthrax

This table was adapted from lnglesby et aI.

Type of Therapy	Adults (including pregnant women and the immunocompromised)	Children
Initial therapy	Ciprofloxacin, 400 mg IV, every 12 hours*	Ciprofloxacin, 20-30 mg/kg of body weight per day IV, divided into 2 daily doses
Optimal therapy of the strain has proved susceptible	Penicillin G, 4 million U IV every 4 hours	Ciprofloxacin, 20-30 mg/kg of body weight per day IV, divided into 2 daily doses
	Doxycycline, 100 mg IV every 12 hours	Penicillin G, 50,000 U/kg IV every 6 hours in children <12 years old; 4 million U IV every 4 hours in children >12 years old
Consider dual therapy **

Oral antimicrobial therapy may be substituted for intravenous (IV) therapy when clinical status has improved. Doxycycline can also be used in children when the use of ciprofloxcin and penicillin is precluded by the results of susceptibility testing, drug hypersensitivity, or the exhaustion of drug supplies. The adult dosage may be used for those weighing more than 45kg; for those weighting 45k or less, the dose should be 2.2 mg per kilogram of body weight given intravenously every 12 hours. The total duration of treatment (initial therapy plus subsequent optimal therapy) should be 60 days.

*As an alternative, ofloxacin, 400 mg given intravenously every 12 hours, or levofloxacin 500 mg given intravenously every 24 hours, can be used.

**The use of dual initial therapy (ciprofloxacin plus penicillin) may be considered, in view of the frequent and rapid development of complicating meningitis and the clinical experience of cerebrospinal-fluid penetration with high-dose intravenous penicillin.

Most recent CDC recommendations for treatment of inhalational anthrax involve the initial use of either ciprofloxcin or doxycycline plus one or two additional antimicrobial agents with in vitro activity against B. anthracis. Because preliminary data have shown the presence of constitutive and inducible beta-lactamases in recent B. anthracis isolates from Florida, New York, and Washington D.C., treatment of systemic anthrax with penicillin G, ampicillin, or amoxicillin alone is not recommended.

Treatment with antimicrobial drugs is not warranted for asymptomatic persons unless public health or law enforcement authorities have ascertained that there is an evident risk of exposure to a substance documented to be anthrax. Indeed, the prolonged unnecessary use of antibiotics may be deleterious since it may encourage the selection of resistant strains of commensals.

A long period of prophylaxis is recommended because of the latency period that may elapse before the germination of spores. Because of the threat of a bioterrorist attack and because a strain of B. anthracis has been produced overseas that is resistant to multiple antibiotics (penicillin, doxycycline, chloramphenicol, macrolides, and rifampin), ciprofloxacin is the drug of choice for initial therapy.

Prophylaxis

Recommendations for post exposure prophylaxis:

This table was adapted from lnglesby et al. and CDC guidelines.

Type of Therapy	Adults (including pregnant women and the immunocompromised)	Children
Initial therapy	Ciprofloxacin, 500 mg orally every 12 hours OR Doxycycline, 100 mg IV every 12 hours	Ciprofloxacin, 10-15 mg/kg of body weight orally every 12 hours OR Doxycycline, 100 mg orally twice a day in children >8 yr old and > 45 kg
Optimal therapy of the strain has proved susceptible	Amoxicillin, 500 mg orally every 8 hours OR Doxycycline, 100 mg orally every 12 hours	Amoxicillin, 500 mg orally every 8 hours in children > 20 kg; 40 mg/kg orally, divided into 3 doses (every 8 hours), in children <20 kg.

Although fluoroquinolones (including ciprofloxacin) are not recommended for use during pregnancy, because of an association with arthropathy in young animals and children, the possible risk of engineered antibiotic-resistant strains warrants the initial use of ciprofloxacin in exposed pregnant women. Although tetracyclines (including doxycycline) have been associated with hepatotoxicity in pregnant women and adverse effects on the developing teeth and bones of fetuses, the initial use of doxycycline is recommended in view of the potential for life-threatening illness when the use of penicillin and ciprofloxacin is precluded by the results of antimicrobial susceptibility testing, drug allergy, or the exhaustion of drug supplies. The use of tetracyclines and fluoroquinolones in children has adverse effect, and these must be weighed carefully against the risk of life-threatening anthrax infection. The total duration of treatment (initial therapy plus subsequent optimal therapy) should be 60 days.

Control Measures and Decontamination

1. Isolation

Standard Precautions are sufficient for patient care since person-to-person transmission has not been shown to occur. Contact Precautions should be used with patients who have draining cutaneous lesions.

2. Environmental Surfaces

a. Diagnosed Cases

Patient care areas of diagnosed cases with cutaneous, gastrointestinal or inhalation Anthrax: Routine cleaning with hospital grade disinfectant.

b. Initial Exposure

Patient care areas of persons with initial exposure to Anthrax spores and visible contamination. The decon shower area should be disinfected by a hospital grade sporicidal solution or a 1:10 bleach solution after the individual has removed clothing and showered (clothing should have been bagged — see Handling Suspicious Substances).

c. Scene of Exposure

At the initial scene of the exposure following credible threats: Guidance for environmental cleanup and decontamination will be provided by the Health Department and! or EPA for individual cases (see Handling Suspicious Substances).

Notification

Internal: At hospital notify

External: All suspected cases of Anthrax exposure are Class Al Reportable and should be reported immediately to the Local Health Department who will then contact the State Health Department and/or CDC.

Lab

Due to potential risks associated with handling infectious materials, laboratory testing should be the minimum necessary for diagnostic evaluation and patient care. Laboratory specimens should be placed in plastic bags that are sealed, and then transported in clearly labeled, durable, leak-proof containers directly to the specimen handling area of the laboratory. Care should be taken not to contaminate the external surfaces of the container. Lab personnel should be notified of what they are handling. Bio-Safety Level 2 should be used for handling specimens.

SEND ALL SPECIMENS TO MICROBIOLOGY LAB; DO NOT USE TUBE SYSTEM

Anthrax	Blood Cultures: two separate sets from different sites (one set is 2 bottles – 10 ml each bottle)	Lavender Tube (EDTA) (for inpatients only) (or direct gram stain)	2 red-top or gold-top tubes (for PCR and acute serology)	Sputum	Pleural fluid (if present)	CSF (if meningeal signs present)	Cutaneous Lesions: swabs X 2 and punch biopsies X 3 (see notes below)	Stool (not in transport medium)	Anterior Nares Swab	ID Consult	Note under comments on microbiology requisition
Possible B. Anthracis	No	No	No	No	No	No	No	No	No	No	Not applicable
Anthrax – inhalational	Yes	Yes	Yes	Yes	Yes	Yes	No	No	No	Yes	R/O Anthrax
Anthrax cutaneous – vesicular stage	Yes	Yes	Yes	No	No	No	See notes below	No	No	Yes	R/O Anthrax
Anthrax cutaneous – eschar stage	Yes	Yes	Yes	No	No	No	See notes below	No	No	Yes	R/O Anthrax
Anthrax – GI	Yes	Yes	Yes	No		No	No	Yes	No	Yes	R/O Anthrax

Notes regarding cutaneous Lesions:

1. Swabs

a. Vesicular lesions – soak 2 swabs (1 culture swab) in previously unopened vesicle fluid and send to micro lab

b. Eschar lesions – rotate 2 swabs (1 culture swab) beneath edge of eschar without removing eschar and send to micro lab

2. Punch biopsies

a. Send one is sterile saline for culture

b. Send one in 10% formaline to be sent to CDC for histopathology and immunohistochemical staining

c. Send one in a sterile cup to be frozen and sent to CDC for culture and PCR

References:

Inglesby TV, Henderson DA, Bartlett JO, et al. Anthrax as a biological weapon: medical and public health management. JAMA 1999; 281:1735-45 (Erratum, JAMA 2000; 283: 1963.)

Notice to Readers: Considerations for Distinguishing Influenza-like Illness from lnhalational Anthrax MMWR 2001; 50(44); 984-6

Ohio Department of Health 10/24/01 written communication from Forrest Smith

New York City Department of Health website

Swartz, Morton N. Recognition and Management of Anthrax-An Update. New England Journal of Medicine 2001 Vol. 345 November 29,2001 No. 22

Update: investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR 2001; 50:909-19.

Also available at http://www.bt.cdc.gov/agent/anthrax/index.asp

Anthrax as a Biological Weapon: Medical & Public Health Management JAMA, May12, 1999 Vol. 281, no.18, 1735-1745.

CDC, MMWR Weekly Report, Nov.9, 2001, 50(44); 984-6 MMWR November 9, 2001 50(44); 984-6

CDC Website

Note: These are guidelines that have been developed with data available as of 1/21/02.

Initially Prepared by

The Akron Regional Hospital Association

Emergency Preparedness Subcommittee

August 20, 2002