Missouri Department of Health

Missouri Department of Health & Senior Services

FROM: MAUREEN E. DEMPSEY, M.D.

DIRECTOR, Missouri Department of Health and Senior Services

SUBJECT: ANTHRAX PROPHYLAXIS, TREATMENT, AND REPORTING GUIDELINES

DATE: October 28, 2001

*** Urgent Notice ***

It is critically important to widely distribute this update to Physicians, Emergency Medicine Directors, Urgent Care Centers and Infection Control Practitioners.

Due to the confirmed cases of inhalation and cutaneous anthrax in several East coast states, individuals concerned that they have been exposed to anthrax are seeking testing and treatment from physicians and emergency departments.

The Department of Health and Senior Services (DHSS) provides the following information to assist in the diagnosis and management of concerned or potentially exposed individuals. Please contact the Department if you have any questions at 1-800-392-0272.

Reporting

The Missouri Department of Health & Senior Services requests immediate reporting of any suspected or confirmed cases of anthrax and potential exposures to anthrax to the local public health agency or the Department (800/392-0272). This includes reporting of individuals who request and receive prophylaxis or treatment due to concerns regarding anthrax, without a known exposure.

As of 10/28/01, NO cases of anthrax have been confirmed in Missouri. Should an anthrax case be confirmed in Missouri, testing and prophylaxis protocols for affected individuals will be widely distributed, as has occurred with persons exposed in the governmental buildings and U.S. Postal Service facilities. Health Alerts are sent regularly to all Missouri hospitals, to local public health agencies and to many Missouri medical professional agencies. In addition, they are routinely updated and listed on the DHSS web site (http://www.dhss.state.mo.us/BT_Response/BT_Response.html).

To date, the confirmed anthrax exposures and illnesses have occurred among postal workers and others opening mail targeted to individuals in high profile governmental and media positions. There must be a high index of suspicion for anthrax illness among employees who are in the following risk groups: postal workers, mail handlers, and those who work in high profile governmental and media offices. Clinicians evaluating patients who report a possible exposure to anthrax should assess the individual’s risk of exposure by inquiring about their occupation and specific work duties, and may receive assistance in determining other plausible anthrax exposure situations in consultation with the public health department.

Risk Stratification and Management

Below are several scenarios that help to define level of risk and determine methods of diagnosis. Guidelines for appropriate post-exposure prophylaxis and presumptive treatment are included.

Note: In the absence of a credible threat of anthrax exposure, the Department strongly recommends against:

Using nasal swabs as a diagnostic tool for anthrax exposure. Nasal swabs are used as an epidemiological tool only when a known exposure has occurred.
Prescribing prophylactic antibiotics for the general public.

Scenario 1:

ASYMPTOMATIC individual

NO exposure to proven anthrax source:

ASSESS: Clinicians treating patients who fear they may have been exposed to anthrax should assess the individual’s risk of exposure including place of employment and specific work duties.

High risk groups for anthrax include high profile governmental and media positions and their employees, mail handlers and postal workers.

DO NOT SCREEN: No screening test is available for the detection of anthrax exposure in an asymptomatic person. Nasopharyngeal (NP) swabs and blood serum tests should NOT be used for screening or diagnosis.

REASSURE: Provide reassurance to the patient about the rarity of anthrax infection without known exposure to anthrax.

Prophylaxis or treatment is not necessary.

REPORT: Report concerned individuals seeking prophylaxis or treatment to the local public health agency or Missouri DHSS at (1-800-392-0272). The Missouri DHSS, in conjunction with the CDC, will provide updated information regarding additional high risk groups identified in other proven exposures or through local/regional epidemiological studies.

Scenario 2:

ASYMPTOMATIC individual

EXPOSURE to proven anthrax source:

ASSESS: Clinicians treating patients who fear they may have been exposed to anthrax should assess the individual’s risk of exposure including place of employment and specific work duties.

High risk groups for anthrax include high profile governmental and media positions and their employees, mail handlers and postal workers.

DO NOT SCREEN: No screening test is available for the detection of anthrax exposure in an asymptomatic person. Nasopharyngeal (NP) swabs and blood serum tests should NOT be used for screening or diagnosis.
Missouri DHSS, in conjunction with CDC, will provide guidance and direction for screening for epidemiological purposes in the event of major exposure events, such as have occurred in Florida, New Jersey and Washington, DC.

PROPHYLAXIS: Post-exposure prophylaxis is indicated in order to prevent inhalational anthrax following a suspected or confirmed aerosol exposure to B. Anthracis, as provided below in Table 1.

TABLE 1. Interim recommendations for postexposure prophylaxis for prevention of inhalational anthrax after intentional exposure to Bacillus anthracis

Category Initial therapy Duration

Adults (including pregnant women Ciprofloxacin 500 mg po BID 60 days

and immunocompromised persons) or

Doxycycline 100 mg po BID

Children Ciprofloxacin 10-15 mg/kg po Q12 hrs* 60 days

Doxycycline:

>8 yrs and >45 kg: 100 mg po BID

>8 yrs and < or equal to 45 kg: 2.2 mg/kg po BID

< or equal to 8 yrs: 2.2 mg/kg po BID

*Ciprofloxacin dose should not exceed 1 gram per day in children.

Postexposure prophylaxis is indicated to prevent inhalational anthrax after a confirmed or suspected aerosol exposure. When no information is available about the antimicrobial susceptibility of the implicated strain of B. anthracis, initial therapy with ciprofloxacin or doxycycline is recommended for adults and children (Table 1). Use of tetracyclines and fluoroquinolones in children has adverse effects. The risks for these adverse effects must be weighed carefully against the risk for developing life-threatening disease. As soon as penicillin susceptibility of the organism has been confirmed, prophylactic therapy for children should be changed to oral amoxicillin 80 mg/kg of body mass per day divided every 8 hours (not to exceed 500 mg three times daily). B. anthracis is not susceptible to cephalosporins or to trimethoprim/sulfamethoxazole, and these agents should not be used for prophylaxis.

Source: MMWR Vol. 50/No. 41, 10/19/01

Guidelines for prophylaxis of asymptomatic individuals are also available on the Missouri Department of Health and Senior Service (DHSS) website: http://www.dhss.state.mo.us/BT_Response/BT_Response.html and on the Centers for Disease Control website at (www.cdc.gov).

REPORT: Report individuals who have suspected or confirmed aerosol exposure to anthrax to the Missouri DHSS at (1-800-392-0272).

Scenario 3:

SYMPTOMATIC individual

EXPOSURE to proven anthrax source

OR differential diagnosis includes anthrax infection

ASSESS: Clinicians treating patients who fear they may have been exposed to anthrax should assess the individual’s risk of exposure including place of employment and specific work duties.

High risk groups for anthrax include high profile governmental and media positions and their employees, mail handlers and postal workers.

Determine if history, signs and symptoms are compatible with anthrax infection. See Attachment A.

TREAT: Presumptive therapy is indicated pending diagnostic tests for patients with illness compatible with anthrax, as provided in Tables 2 and 3 which follow on next pages.
Therapy for patients with presumed anthrax can be modified after several days based upon epidemiological information provided through consultation with public health officials and by confirmatory laboratory tests.

REPORT: Report individuals receiving presumptive therapy for anthrax infection to the Missouri DHSS at (1-800-392-0272).

REFER for environmental testing: Determine if an environmental sample of the exposure substance is available. If so, refer to local law enforcement as noted below.

TABLE 2. Inhalational anthrax treatment protocol*^,+ for cases associated with the

bioterrorism attack

Category	Initial therapy (intravenous)^#,~	Duration
Adults	Ciprofloxacin 400 mg every 12 hrs* or Doxycycline 100 mg every 12 hrs⁺⁺ and One or two additional antimicrobials^~	IV treatment initially**. Switch to oral antimicrobial therapy when clinically appropriate: Ciprofloxin 500 mg po BID Or Doxycycline 100 mg po BID Continue for 60 days (IV and po combined)^##
Children	Ciprofloxacin 10-15 mg/kg every 12hrs^~~,*** or Doxycycline.^+++,++ >8 yrs and >45 kg: 100 mg every 12 hrs >8 yrs and < or equal to 45 kg: 2.2 mg/kg every 12 hrs < or equal to 8 yrs: 2.2 mg/kg every 12 hrs and One or two additional antimicrobials^~	IV treatment initially. Switch to oral antimicrobial therapy when clinically appropriate: Ciprofloxacin 10-15 mg/kg po every 12 hrs* Or Doxycycline⁺⁺⁺ >8 yrs and >45 kg: 100 mg po BID >8 yrs and less than or equal to 45 kg: 2.2 mg/kg po BID less than or equal to 8 yrs: 2.2 mg/kg po BID Continue for 60 days (IV and po combined)^##
Pregnant women^~~~	Same for nonpregnant adults (the high death rate from the infection outweighs the risk posed by the antimicrobial agent)	IV treatment initially. Switch to oral antimicrobial therapy when clinically appropriate.⁺ Oral therapy regimens same for nonpregnant adults.
Immunocompromised persons	Same for nonimmunocompromised persons and children	Same for nonimmunocompromised persons and children

___________________________________________________________________________________________

* For gastrointestinal and oropharyngeal anthrax, use regimens recommended for inhalational anthrax.

+ Ciprofloxacin or doxycycline should be considered an essential part of first-line therapy for inhalational anthrax.

# Steroids may be considered as an adjunct therapy for patients with severe edema and for meningitis based on experience with bacterial meningitis of other etiologies.

~ Other agents with in vitro activity include rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin. Because of concerns of constitutive and inducible beta-lactamases in Bacillus anthracis, pencillin and ampicillin should not be used alone. Consultation with an infectious disease specialist is advised.

** Initial therapy may be altered based on clinical course of the patient; one or two antimicrobial agents (e.g., ciprofloxacin or doxycycline) may be adequate as the patient improves.

++ If meningitis is suspected, doxycycline may be less optimal because of poor central nervous system penetration.

## Because of the potential persistence of spores after an aerosol exposure, antimicrobial therapy should be continued for 60 days.

~~ If intravenous ciprofloxacin is not available, oral ciprofloxacin may be acceptable because it is rapidly and well absorbed from the gastrointestinal tract with no substantial loss by first-pass metabolism. Maximum serum concentrations are attained 1-2 hours after oral dosing but may not be achieved if vomiting or ileus are present.

*** In children, ciprofloxacin dosage should not exceed g/day.

+++ The American Academy of Pediatrics recommends treatment of young children with tetracyclines for serious infections (e.g., Rocky Mountain spotted fever)

~~~ 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 time (7-14 days) before 6 months of qestation. Source: MMWR Vol. 50/No 42, 10/26/01

TABLE 3. Cutaneous anthrax treatment protocol* for cases associated with the bioterrorism attack

Adults* Ciprofloxacin 500 mg BID 60 days^#

Doxycycline 100 mg BID

Children* Ciprofloxacin 10-15 mg/kg every 12 hrs 60 days^#

(not to exceed 1 g/day)⁺

Doxycycline^~

>8 yrs and >45 kg: 100 mg every 12 hrs

>8 yrs and < or equal to 45 kg: 2.2 mg/kg every 12 hrs

< or equal to 8 yrs: 2.2 mg/kg every 12 hrs

Pregnant women*^,** Ciprofloxacin 500 mg BID 60 days^#

Doxycycline 100 mg BID

Immunocompromised Same for nonimmunocompromised persons 60 days^#

Persons* and children

_________________________________________________________________________________________________

* Cutaneous anthrax with signs of systemic involvement, extensive edema, or lesions on the head or neck requires Intravenous therapy, and a multidrug approach is recommended. Table 2

+ Ciprofloxacin or doxycycline should be considered first-line therapy. Amoxicillin 500 mg po TID for adults or: mg/kg/day divided every 8 hours for children is an option for completion of therapy after clinical improvement. Oral amoxicillin dose is based on the need to achieve appropriate minimum inhibitory concentration levels.

# Previous guidelines have suggested treating cutaneous anthrax for 7-10 days, but 60 days is recommended in the setting of this attack, given the likelihood of exposure to aerosolized B. anthracis (6).

~ The American Academy of Pediatrics recommends treatment of young children with tetracyclines for serious infections (e.g., Rocky Mountain spotted fever).

** Although tetracyclines or ciprofloxacin 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 time (7-14 days) before 6 months of gestation.

Source: MMWR Vol. 50/No 42, 10/26/01

Scenario 4:

SYMPTOMATIC individual

EXPOSURE to potential anthrax source via an unknown substance:

OR differential diagnosis includes anthrax infection

ASSESS: Clinicians treating patients who fear they may have been exposed to anthrax should assess the individual’s risk of exposure including place of employment and specific work duties.

High risk groups for anthrax include high profile governmental and media positions and their employees, mail handlers and postal workers.
Determine if history, signs and symptoms are compatible with anthrax infection. See Attachment A.

TREAT: Presumptive therapy is indicated pending diagnostic tests for patients with illness compatible with anthrax, as provided in Tables 2 and 3.
Therapy for patients with presumed anthrax can be modified after several days based upon epidemiological information provided through consultation with public health officials and by confirmatory laboratory tests.

REPORT: Patients receiving presumptive therapy for anthrax should be reported to the Missouri DHSS at (1-800-392-0272).

REFER for environmental testing: Determine if an environmental sample of the exposure substance is available. If so, refer to local law enforcement as noted below.

Clinical and Environmental Samples

Clinical samples can be obtained by the individual’s personal physician or in the Emergency Department and may be processed and analyzed through clinical laboratories routinely utilized by those providers or facilities. Specialized tests, such as PCR, Immunoflourescence and Immunohistochemistry can be arranged through the Missouri DHSS, if indicated.

Evaluation of potential anthrax exposure is the dual responsibility of law enforcement and public health officials. If environmental samples from suspicious sources (such as powders from letters) are available, local law enforcement will work with the FBI and local/regional HAZMAT (hazardous materials) Teams to assess the environmental situation. They will obtain environmental samples and prepare them for transport to the State Public Health Laboratory for analysis. Refer to Health Alert #10 for specific protocols and procedures.

Attachment A

CUTANEOUS ANTHRAX

Route of Transmission:

Deposition of organism onto exposed skin through scratches, abrasions or open wounds.

Incubation:

1-12 days

Signs and Symptoms:

Papule progresses through to a vesicular stage (~ day 2)
Vesicular stage progresses to a black necrotic ulcer – eschar (~ day 10)
Redness and/or necrosis without ulceration may occur
Heaped border /vesicular ring
Painless
Pruritic
Edema of affected area or limb may be prominent

Differential Diagnosis:

Spider bite
Ecthyma gangrenosum
Ulceroglandular tularemia
Plague
Staphylococcal or streptococcal cellulitis

Diagnosis:

Charactersistic eschar
Gramstain and culture of vesicular fluid
Blood culture
Biopsy
PCR (blood)*

Immunoflourescence, Immunohistochemistry*

* Must be arranged with Missouri Department of Health and Senior Services

(800/392-0272)

Treatment:

SEE TABLE 3 CUTANEOUS ANTHRAX TREATMENT PROTOCOL

ANY CHANGES IN TREATMENT PROTOCOLS WILL BE POSTED ON OUR WEB SITE AT www.dhss.state.mo.us

Report any suspected or confirmed case of anthrax to the local public health agency or the Missouri Department of Health and Senior Services (800/392-0272).

Attachment A

INHALATIONAL ANTHRAX

Route of Transmission:

Inhalation of 8,000 – 40,000 spores

Spores engulfed by macrophages and transported to mediastinal and peri-bronchial lymph nodes

Incubation:

2 – 3 days (may be up to 60 days)

Signs and Symptoms:

Prodrome (2 – 3 days)

Viral-like illness
Insidious onset
Malaise
Myalgia
Fatigue
Low grade fever
Non-productive cough

Followed by:

Abrupt onset of respiratory distress
Dyspnea
Hypoxia
Hemorragic mediastinitis possible
Hematogenous spread probable
Meningitis in 50%, usually fatal

Differential Diagnosis:

Mycoplasma pneumonia
Legionaire’s
Psittacosis
Tularemia
Q fever
Viral pneumonia
Histoplasmosis
Coccidiomycosis

Diagnosis:

Widened mediastinum on CXR
Pleural effusion in 55% of cases
Blood and/or CSF cultures and gram stain
PCR (blood)*
Immunoflourescence, Immunohistochemistry*

* Must be arranged with Missouri Department of Health and Senior Services

(800/392-0272)

Attachment A

Prophylaxis:

SEE TABLE 1 FOR PROPHYLAXIS OF INHALATIONAL ANTRHAX

Treatment:

SEE TABLE 2 Inhalational ANTHRAX TREATMENT PROTOCOL

ANY CHANGES IN TREATMENT PROTOCOLS WILL BE POSTED ON OUR WEB SITE AT www.dhss.state.mo.us

Report any suspected or confirmed case of anthrax to the local public health agency or the Missouri Department of Health and Senior Services (800/392-0272).

GASTROINTESTINAL ANTHRAX

Route of Transmission:

Ingestion of insufficiently cooked contaminated meat from infected animals

Incubation:

1–7 days

Signs and Symptoms:

Oropharyngeal form

Lesions at base of tongue
Dysphagia
Sore throat
Fever
Regional lymphadenopathy

Abdominal form

Nausea
Vomiting
Fever
Loss of appetite
Abdominal pain
Hematemesis
Bloody diarrhea

Diagnosis:

Blood culture
PCR (blood)*

* Must be arranged with Missouri Department of Health and Senior Services

(800/392-0272)

Treatment:

USE REGIMEN RECOMMENDED FOR INHALATIONAL ANTHRAX.

SEE TABLE 2 FOR INHALATIONAL ANTHRAX TREATMENT PROTOCOL.

ANY CHANGES IN TREATMENT PROTOCOLS WILL BE POSTED ON OUR WEB SITE AT www.dhss.state.mo.us

Report any suspected or confirmed case of anthrax to the local public health agency or the Missouri Department of Health and Senior Services (800/392-0272).