Investigation of Bioterrorism-Related Anthrax, 2001 FREE

MMWR. 2001;50:1008-1010

This report updates the investigation of bioterrorism-related anthrax and the provision of antimicrobial prophylaxis to exposed persons and highlights CDC assistance to other countries investigating cases of bioterrorism-related anthrax. Since November 7, 2001, CDC and state and local public health agencies have identified no new cases of bioterrorism-related anthrax. As of November 14, a total of 22 cases of anthrax have met the CDC case definition¹; 10 were confirmed inhalational anthrax, and 12 (seven confirmed and five suspected) were cutaneous anthrax. Investigation of a case of inhalational anthrax in a hospital stock room worker aged 61 years in New York City (NYC) found no evidence of anthrax contamination at the work site or home; the source of exposure is unknown. Environmental clean-up of contaminated facilities continues, and surveillance for new cases of bioterrorism-related anthrax is ongoing in Delaware (DE), District of Columbia (DC), Florida (FL), Maryland (MD), New Jersey (NJ), NYC, Pennsylvania (PA), Virginia (VA), and other states.

A 60-day course of antibiotics to prevent inhalational anthrax has been recommended for persons potentially exposed to Bacillus anthracis aerosols in FL, NJ, NYC, VA, and DC. These recommendations are for persons at risk for inhalational anthrax by (1) the presence of an inhalational case at a facility (e.g., media company in FL), (2) environmental specimens positive for B. anthracis in facilities along the path of a contaminated letter in which aerosolization might have occurred (e.g., postal facilities in NYC), and (3) exposure to an air space known to be contaminated with aerosolized B. anthracis from an opened letter (e.g., Senate office building in DC). These persons should receive a full 60-day course of antimicrobial prophylaxis. Specific recommendations by site include:

In addition, a 60-day course of antimicrobial prophylaxis is recommended for other workers with specified risks for inhalational anthrax. In some areas, local health authorities facilitated access to a 60-day course of antimicrobial prophylaxis for persons who handled mail in facilities from which B. anthracis was isolated but did not have exposures for which antimicrobial prophylaxis is recommended.² These persons may choose or may be directed by local health authorities to discontinue antimicrobial prophylaxis before completing a 60-day course.

CDC has assisted authorities in other countries investigating cases of bioterrorismrelated anthrax. During October 12-November 13, CDC received 111 requests from 66 countries. Of these, 47 (42%) requests were laboratory related; 43 (39%) were general requests for bioterrorism information; 13 (12%) were for environmental or occupational health guidelines; and eight (7%) were about developing bioterrorism preparedness plans. The largest proportion of requests were from Central and South America (26%). Of the 66 countries, 15 (23%) received laboratory assistance, including testing or arrangements for testing of suspected isolates at a CDCsupported laboratory or a reference laboratory in another country. Forty-two (64%) countries received telephone or e-mail consultation regarding specific tests for suspected B. anthracis isolates. CDC has confirmed two isolates from outside the United States as B. anthracis. These isolates were recovered from the outer surface of letters or packages sent in State Department pouches to the U.S. Embassy in Peru. These items were processed at the U.S. State Department mail sorting facility where a case of inhalational anthrax had occurred.¹ No cases of bioterrorism-related anthrax have been confirmed in U.S. Embassy employees or in persons from other countries. Requests for information regarding bioterrorism-related issues outside the United States should be directed to the International Team of CDC's Emergency Operations Center (telephone, [770] 488-7100, e-mail, eocinternational@cdc.gov).

J Malecki, MD, Palm Beach County Health Dept, West Palm Beach; S Wiersma, MD, State Epidemiologist, Florida Dept of Health. New York City Dept of Health. E Bresnitz, MD, State Epidemiologist, G DiFerdinando, MD, New Jersey Dept of Health and Senior Svcs. P Lurie, MD, K Nalluswami, MD, Pennsylvania Dept of Health. L Hathcock, PhD, State Epidemiologist, Delaware Div of Public Health. L Siegel, MD, S Adams, I Walks, MD, J Davies-Coles, PhD, M Richardson, MD, District of Columbia Dept of Health. R Brechner, MD, State Epidemiologist, Maryland Dept of Health and Hygiene. R Stroube, MD, State Epidemiologist, Virginia Dept of Health. J Burans, US Naval Research Center Detachment, Lima, Peru. US Dept of Defense. EIS officers, CDC.

Since the previous report, all patients with bioterrorism-related anthrax who were hospitalized have been discharged and continue to recover; no new cases have been reported. The source of these bioterrorist attacks has not been identified, and additional cases might occur. Public health authorities, health-care providers, and laboratorians should remain vigilant for cases of anthrax.

Antimicrobial prophylaxis is indicated to prevent inhalational anthrax after a confirmed or suspected aerosol exposure. Persons recommended to receive prophylaxis should complete the 60-day regimen. Public health programs should work with health-care providers and patients to promote completion of antimicrobial prophylaxis and to monitor the occurrence of adverse events.¹

CDC continues to respond to inquiries about anthrax and bioterrorism. The CDC Public Response Hotline was established to provide the public with information about anthrax and other biologic and chemical agents. During November 1-12, CDC received approximately 4,400 calls through the hotline and to the Emergency Operations Center. The hotline is available in English (888-246-2675) and Spanish (888-246-2857). CDC also receives requests for information by e-mail through the Health Alert Network (healthalert@cdc.gov), MMWR (http://www.cdc.gov/mmwr/contact.html), and other public health communications systems.

Additional information about anthrax is available at http://www.bt.cdc.gov. A compendium of MMWR reports and recommendations related to anthrax and bioterrorism is available at http://www.cdc.gov/mmwr.

References: 2 available

MMWR. 2001;50:1014-16

Ciprofloxacin or doxycycline is recommended for antimicrobial prophylaxis and treatment of adults and children with Bacillus anthracis infection associated with the recent bioterrorist attacks in the United States. Amoxicillin is an option for antimicrobial prophylaxis for children and pregnant women and to complete treatment of cutaneous disease when B. anthracis is susceptible to penicillin, as is the case in the recent attacks.^1-3 Use of ciprofloxacin or doxycycline might be associated with adverse effects in children,^4,5 and liquid formulations of these drugs are not widely available. This notice provides further information about prophylaxis and treatment of children and breastfeeding mothers, including the use of amoxicillin.

Ciprofloxacin, doxycycline, and penicillin G procaine have been effective as antimicrobial prophylaxis for inhalational B. anthracis infection in nonhuman primates and are approved for this use in humans by the Food and Drug Administration (FDA).^5,6 Amoxicillin has not been studied in animal models and is not approved by FDA for the prophylaxis or treatment of anthrax. Other data indicate that B. anthracis strains produce a cephalosporinase and suggest that the strains contain an inducible beta-lactamase that might decrease the effectiveness of penicillins, especially when a large number of organisms is present.² In addition, penicillin achieves low intracellular concentrations that might be detrimental to its ability to kill germinating spores in macrophages.

Because of these concerns, penicillins (including amoxicillin) are not recommended for initial treatment of anthrax, but are likely to be effective for antimicrobial prophylaxis following exposure to B. anthracis, a setting where relatively few organisms are expected to be present. Therefore, amoxicillin* may be used for the 60-day antimicrobial prophylaxis in infants and children when the isolate involved in the exposure is determined to be susceptible to penicillin. Isolates of B. anthracis implicated in the recent bioterrorist attacks are susceptible to ciprofloxacin, doxycycline, and penicillin.²

Initial treatment of infants and children with inhalational or systemic (including gastrointestinal or oropharyngeal) anthrax should consist of intravenous ciprofloxacin† or doxycyline,‡ plus one or two additional antimicrobial§ agents. If meningitis is suspected, ciprofloxacin might be more effective than doxycycline because of better central nervous system penetration.² Experience with fluoroquinolones other than ciprofloxacin in children is limited.

Ciprofloxacin or doxycycline should be the initial treatment of localized cutaneous anthrax in infants and children. Intravenous therapy with multiple antimicrobial agents is recommended for cutaneous anthrax with systemic involvement, extensive edema, or lesions on the head or neck.² Whether infants and young children are at increased risk for systemic dissemination of cutaneous infection is not known; a 7-month-old patient infected during the recent bioterrorism attacks developed systemic illness after onset of cutaneous anthrax.⁷ For young children (e.g. aged <2 years), initial therapy of cutaneous anthrax should be intravenous, and combination therapy with additional antimicrobials should be considered.

After clinical improvement following intravenous treatment for inhalational or cutaneous anthrax, oral therapy with one or two antimicrobial agents (including either ciprofloxacin or doxycycline) may be used to complete the first 14-21 days of treatment for inhalational anthrax or the first 7-10 days for uncomplicated cutaneous anthrax. The optimal oral treatment regimen is unknown; some adults with inhalational anthrax as a result of the recent bioterrorist attacks are receiving ciprofloxacin and rifampin. For both inhalational and cutaneous anthrax in the setting of this bioterrorist attack, antimicrobial therapy should be continued for 60 days because of the likelihood of exposure to aerosolized B. anthracis and the need to protect against persistent spores that might germinate in the respiratory tract. Because of potential adverse effects of prolonged use of ciprofloxacin or doxycycline in children, amoxicillin is an option for completion of the remaining 60 days of therapy for persons infected in these bioterrorist attacks.

Because of its known safety for infants, amoxicillin is an option for antimicrobial prophylaxis in breastfeeding mothers when B. anthracis is known to be penicillin-susceptible and no contraindication to maternal amoxicillin use is indicated. The American Academy of Pediatrics also considers ciprofloxacin and tetracyclines (which include doxycycline) to be usually compatible with breastfeeding because the amount of either drug absorbed by infants is small, but little is known about the safety of long-term use.⁸ Mothers concerned about the use of ciprofloxacin or doxycycline for antimicrobial prophylaxis should consider expressing and then discarding breast milk so that breastfeeding can be resumed when antimicrobial prophylaxis is completed. Decisions about antimicrobial choice and continuation of breastfeeding should be made by the mother and her and the infant's health-care providers. Consideration should be given to antimicrobial efficacy, safety for the infant, and the benefits of breastfeeding.

Health-care providers prescribing antimicrobial drugs for the prophylaxis or treatment of anthrax should be aware of their adverse effects and consult with an infectious disease specialist as needed. Additional information about recognition, prophylaxis, and treatment of anthrax infection is available at http://www.bt.cdc.gov.

References: 8 available

*The recommended dose of amoxicillin is 80 mg/kg/day orally divided every 8 hours (maximum 500 mg/dose).

†The recommended dose of ciprofloxacin is 10 mg/kg/dose every 12 hours intravenously (maximum 400 mg/dose) or 15 mg/kg/dose every 12 hours orally (maximum 500 mg/dose).

‡The recommended dose of doxycycline is 2.2 mg/kg/dose every 12 hours intravenously or orally (maximum 100 mg/dose).

§Options for additional drugs, based on in vitro sensitivity testing of isolates in the recent attacks, include rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin.²

MMWR. 2001;50:873-874

In December 2000, the Washington State Health Department discovered white powder that was found to be lead oxide in boxes used to store dental intraoral radiograph film. The Washington State Health Department alerted state health departments throughout the United States. Subsequently, the Wisconsin Division of Public Health (WDPH) conducted an investigation of dental offices in the state. This report summarizes the investigation, which indicated that similar storage boxes are used in Wisconsin. The findings indicate that patients are at risk for exposure to a substantial amount of lead during a dental radiograph procedure if the office stores dental film in these boxes.

During January–March 2001, radiation safety inspectors in Wisconsin visited 240 (9%) of 2,748 dental offices with radiograph equipment. Of these, 43 (18%) stored radiograph film in table-top, lead-lined boxes. Of 11 dental offices in use for >20 years, four (36%) used this storage method.

The boxes were usually made of wood and shaped like a shoe box. All boxes contained a white powder residue. A bulk sample of the residue contained 77% lead identified as lead oxide. Visits to dental offices occurred before and after a mailing had been sent by WDPH to all dental offices with radiograph equipment warning about possible lead exposure and recommending that lead-lined storage boxes be discarded. Many offices discarded the boxes before the inspection. In one office, after receiving the warning, paper was placed in the bottom of the box and film was placed on top of the paper. In another office, dental instruments had been placed in the box. Other offices used a vertical wall-mounted, lead-lined film dispensing box. Some of these boxes and the film in them also contained lead.

A mock dental radiograph procedure was performed during which wipes were placed on the tips of a dental hygienist's fingers whenever a patient's mouth was touched. Analysis of these wipe samples found 3,378µg lead that could have been transferred from the hygienist's fingers to a patient's mouth. Lead also could have been introduced directly from the film. Wipe samples of eight film packets from two dental offices that used the lead-lined storage boxes identified average lead levels of 3,352µg (range: 262µg-34,000µg). During a typical radiographic procedure, usually conducted once per year, ≥4 separate views are taken. When children's teeth develop to the point where adjacent teeth touch (usually age 3 years), radiographs may be taken if the dentist suspects decay.

Because of the increased susceptibility of children and the developing fetus,¹ lead exposure is particularly dangerous for children and for women who are or may soon become pregnant. The approximate half-life of lead in blood is 25 days²; as a result, the window for identifying lead exposure following dental radiographs is a few months. Health-care providers who discover high blood lead levels of unexplained origin should consider this possible route of exposure.

Advances in dental radiograph technology have reduced scatter radiation—the reason for protective boxes—making lead-lined radiograph storage boxes unnecessary. Because lead oxide cannot be removed adequately, the film packets stored in lead-lined boxes and the film packets stored in them should be discarded.

M Chamberlain, M Bunge, W Otto, HA Anderson, MD, State Epidemiologist, Bur of Environmental Health; N McKenney, MS, W LeMay, DDS, Wisconsin Div of Public Health. Lead Poisoning Prevention Br, Div of Environmental Hazards and Health Effects, National Center for Environmental Health; and an EIS Officer, CDC.

References: 2 available