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This information was originally developed 11/02/01 from resources available on that date. Because of the lack of clinical studies on anthrax in children, the knowledge base is in a state of flux. The AAP and the CDC are working together on a daily basis to make certain that the most appropriate and up to date recommendations are used to care for children who may or have been exposed to anthrax. The AAP will continue to update this information as new material becomes available. IN ALL CASES, CONCERNS OF ANTHRAX EXPOSURE OR INFECTION MUST BE REPORTED TO AND DISCUSSED WITH THE LOCAL PUBLIC HEALTH DEPARTMENT. Additional information is available on the website of the Centers for Disease Prevention and Control (CDC) (http://www.bt.cdc.gov) and in the latest editions of Morbidity and Mortality Weekly Reports (http://www.cdc.gov/mmwr). Background Anthrax bacteria (Bacillus anthracis), non-motile gram-positive capsular rods, are being used as a biologic weapon for terrorism. Inhaled anthrax spores can produce a lethal infection despite antibiotic therapy. Inhalation is promoted when the spores are chemically treated to prevent agglutination and suspended in a powder. In addition, the spores, which remain viable for years, can be easily stored and transported. The clinical signs of anthrax infection and high mortality of inhalation anthrax despite antibiotic treatment are related to the production and release of toxin. The toxin has 3 components; edema factor (EF), lethal factor (LF) and protective antigen (PA) which facilitates the transfer of EF and LF into cells. LF destroys cells and produces local vascular injury, platelet and leucocytic adherence and thrombosis. Work is rapidly progressing to develop an antitoxin treatment that will absorb circulating toxin and or block its attachment to cells. Prior to its use as an agent in bioterrorism, naturally occurring infection was a rare event that required direct contact with spores from infected animals or their products such as goat hair. There has been no evidence for human to human transmission and naturally occurring pediatric infections are even more uncommon than adult infections. Our understanding of pediatric risk factors, clinical presentations, and optimal management (prevention and treatment) of these infections is limited and will evolve with increasing experience and research. Therefore, the information contained in this review is subject to change as new information becomes available. Key aspects of the history and physical examination In the history ask if the child, parent or any relative was diagnosed with an anthrax infection or visited an area with a known exposure or contamination with anthrax spores. It is important to determine whether there has been a credible “known” exposure to anthrax. Carefully document “person, place and time” issues related to a possible exposure. Who worked or visited the location with possible contamination? How well documented is the contamination in the location in question? What specific contaminated areas were visited by the person? How extensive was the contamination in the location? What was the timing of visit to the location? Was it an occasional/ infrequent visit or daily work exposure? Determine if the child visited the location and for how long. Ask about the possibility that the child could have come into contact with clothes or other materials that came into contact with anthrax spores. Ask if the child has systemic symptoms such as fever, malaise, anorexia, or fatigue; respiratory symptoms such as a cough or difficulty breathing, gastrointestinal symptoms such as pain with swallowing, abdominal pain, vomiting or diarrhea, or new skin lesions that look like an insect or spider bite. During the physical examination obtain vital signs and assess the child’s neurologic, circulatory, and respiratory status. Note signs of altered mental status, seizures and focal neurologic findings that suggest sepsis, shock and or meningitis. Count the child’s respirations for 1 minute and look for agitation or restlessness, chest indrawing or retractions, nasal flaring, pallor, cyanosis. Note grunting, hoarseness, stridor, wheezing, rales, crepitations, or decreased air exchange. Note erythema, edema and any skin lesions (papules, vesicles, bullae) and recognize that a painless black eschar bordered by vesicles is very suggestive of cutaneous anthrax. It is important to discuss the history and physical examination findings with the Public Health Department who will help determine whether there is a need for prophylaxis or treatment with antibiotics. Diagnostic testing Contact your local public health authorities if your suspicion of anthrax exposure or disease is high. They will assist in determining what is the best method(s) for evaluation and diagnosis. In consultation with your local public health authorities, consider the most appropriate methods to confirm an anthrax exposure and or infection. Nasal swabs have been used as an epidemiologic tool to document sites of contamination and sphere of exposure, but their value in the diagnosis of an individual case with credible exposure or compatible clinical syndrome is limited. It is important to remember that nasal swab cultures are not sensitive, so that a negative nasal swab culture does not rule out exposure to anthrax. If you are going to send specimens, notify your microbiology laboratory that you are concerned about anthrax. In a symptomatic case, obtain specimens from affected tissue or an involved site ( skin lesion, blood, CSF, or pleural fluid ) for culture and other diagnostic tests such as PCR (polymerase chain reaction) and immunohistochemical staining procedures. Consider performing PCR test on clinical specimens to document the presence of anthrax DNA. Serology testing which usually involves 2 sequential tests may confirm an infection in antibiotic treated culture negative cases. Antibiotic prophylaxis Prophylaxis recommendations have been changing rapidly, so check with public health officials or a pediatric infectious disease specialist prior to initiating therapy. Also, consult the CDC Web site (http://www.bt.cdc.gov) and the most recent issue of MMWR (http://www.cdc.gov/mmwr) for updates. With the advice of public health officials, treat with antibiotics to prevent infection when a child has a credible exposure with an item or environment that is known to be contaminated with anthrax bacterial spores. Treat children whose parents or caregivers have had anthrax isolated from anasal swab or whose parents have clinical signs suggesting cutaneous or inhalation infection regardless of their exposure history. Since at this time there have been no reported cases of secondary spread from materials brought home, it is not necessary to treat children of all parents who are taking antibiotic prophylaxis. Ciprofloxacin, doxycycline, and penicillin G procaine have been tested as prophylactic agents to prevent inhalation anthrax in nonhuman primates and are approved by the FDA for this purpose. Amoxicillin has not been studied in animal models, and its use is not approved by the FDA. Penicillins, including amoxicillin, are not recommended for the initial treatment of clinical disease caused by anthrax; because anthrax strains may have an inducible beta-lactamase that would reduce the effectiveness of penicillins, and the intracellular concentrations achieved by penicillin may be inadequate to kill germinating spores in macrophages. Nevertheless, penicillins, including amoxicillin, are likely to be effective for post-exposure prophylaxis in a setting where few organisms are expected to be present and the anthrax strain involved in the exposure is susceptible to penicillin. Isolates involved in the recent bioterrorist attacks are susceptible to penicillin. Therefore, amoxicillin is considered an option for antimicrobial prophylaxis in children. Initiate antibiotic prophylaxis in children with ciprofloxacin (10-15 mg/kg/dose po q 12 hrs not to exceed 1 gram per day) or doxycycline [up to and including 8 years or over 8 years and less than or equal to 45 kg (2.2 mg/kg/dose po BID)]; [over 8 years and greater than 45 kg (100 mg po BID)] when information on antibiotic susceptibility is not available. When penicillin susceptibility is confirmed initiate or change to oral amoxicillin 80 mg/kg/day TID (maximum 500 mg/dose). Treat children for 60 days in order to insure that spores have had time to germinate and be eradicated. On
12/18/01, the Department of Health and Human Services released a statement defining
Reassurance in absence of anthrax exposure and disease Discuss with families that giving antibiotics to a child who has not been examined by a physician could do more harm than good, since it could mask symptoms of other serious illnesses. In addition, widespread use of these antibiotics will lead to drug-resistant bacteria, which could make the medicines ineffective for those who truly need them. Reassure parents that they can rely on pediatricians and public health officials to advise them of treatment options in the event of exposure in their community. Remind parents that the American Academy of Pediatrics (AAP) and the CDC recommend that they do not obtain antibiotics for their children, either through prescriptions or any other means, unless their pediatrician or public health authorities have told them to do so in the face of documented exposure to anthrax. Reassure parents that symptoms such as fever, body aches, and headaches are common to many different infections besides anthrax. Influenza and other viral infections can also cause cough fever, headache malaise and myalgias. Since the majority of such illnesses are not caused by influenza (or anthrax), influenza vaccination will not prevent many such cases of illness. Therefore, influenza vaccination should not be considered a way to avoid confusing influenza disease with suspected anthrax illness. In addition, influenza vaccine is not 100% protective and some people who have been vaccinated will still develop influenza. If people who have received influenza vaccine develop flu-like symptoms, it will still be much more likely they have another virus infection or even influenza than anthrax. Diagnosis and management of anthrax syndromes Treatment recommendations have been changing rapidly, so check with public health officials or a pediatric infectious disease specialist when initiating therapy. Check the CDC Web site (http://www.bt.cdc.gov) and the most recent issue of MMWR (http://www.cdc.gov/mmwr) for updates. Cutaneous anthrax, the most common anthrax infection syndrome, occurs when spores are inoculated into the skin through minor abrasions, cuts, or scratches. After an incubation period of 12 hours to 12 days the spores germinate, multiply and produce a toxin that causes an initial lesion resembling a pimple or insect bite. Erythema usually surrounds the lesion and satellite vesicular or bullous lesions often develop. Vesicular fluid becomes dark (blue-black) over several days and by the 5th to 7th day the lesion becomes a painless black eschar. (SEE BELOW) Blood dissemination (bacteremia) can lead to sepsis and meningitis. Additional complications of cutaneous anthrax include DIC (disseminated intravascular coagulation) with thrombocytopenia and anemia, severe edema (malignant edema) usually involving the face and neck, and secondary bacterial infections causing lymphadenitis or cellulitis. Notify public health officials and hospitalize children with extensive or severe cutaneous disease (including all children with disease involving the head or neck) for their initial management. Treat uncomplicated cases in children two years or older with PO ciprofloxacin or doxycycline. Because it is not known whether infants are at greater risk of systemic dissemination of cutaneous anthrax, initiate treatment for children younger than two years intravenously and consider combination therapy. If complications are present (eg, systemic involvement, extensive edema, or lesions of the head or neck), treat intravenously with multiple antibiotics as recommended for inhalation anthrax. The case-fatality rate is reduced from 20% in untreated cases to <1% in cases of cutaneous anthrax treated early with antibiotics. (See also MMWR treatment table for cutaneous anthrax)
Inhalation
or pulmonary anthrax results from the inhalation
of anthrax spores 1-5 microns in diameter. Typically the incubation period is
1 to 7 days, but may be as long as 60. Children present with nonspecific
respiratory symptoms of cough associated with low-grade fever, fatigue, malaise,
and muscle aches. Later respiratory distress becomes rapidly progressive and is
often accompanied by a high fever and signs of systemic toxicity (sepsis and or
meningitis). Chest radiographs reveal mediastinal widening often associated with
patchy infiltrates and pleural effusions. (SEE BELOW)
Hospitalize these children in an ICU. Current recommendations are to treat inhalation
anthrax with IV ciprofloxacin or doxycycline plus one or two of the following
antibiotics: rifampin, vancomycin, penicillin, ampicillin, imipenem, chloramphenicol,
clindamycin, and clarithromycin. Ciprofloxacin may be preferred
over doxycycline if meningitis is suspected, because of its better penetration
of the central nervous system. Because of concerns about beta-lactamases,
penicillin or ampicillin should not be used alone to treat severe forms of anthrax.
(See also MMWR
treatment table for inhalation anthrax) Gastrointestinal
anthrax, less common than cutaneous or inhalation
syndromes, results from the ingestion of anthrax spores. In the past this syndrome
was related to eating raw or undercooked contaminated meat. The spores germinate
in the abdominal lymph nodes where they produce a hemorrhagic lymphadenitis and
bacteremia. This syndrome initially presents with generalized abdominal pain,
nausea, vomiting and anorexia followed by the development of bloody diarrhea and
signs of systemic toxicity (sepsis, shock and meningitis), and antibiotic treatment
recommendations are the same as those for inhalation anthrax. Treatment
following clinical improvement. Oral antibiotics may be substituted for intravenous
therapy once clinical improvement is well-established. A regimen of two antibiotics
to include either ciprofloxacin or doxycycline is recommended and continued for
14-21 days for inhalational anthrax and 7-10 days for uncomplicated cutaneous
anthrax. Antimicrobial therapy is recommended for a total of 60 days to protect
against disease that might be caused by the germination of persistent spores in
the respiratory tract. To avoid potential adverse effects from extended use of
ciprofloxacin or doxycycline in children, oral amoxicillin is an option for completion
of the 60 days (see antibiotic prophylaxis above). CDC. Update: investigation of anthrax associated with intentional exposure
and interim public health guidelines, October 2001. MMWR Morb Mortal Wkly Rep.
2001; 50(41):889-893. CDC. Recognition of illness associated with the intentional
release of a biologic agent. MMWR Morb Mortal Wkly Rep. 2001; 50(41):893-897.
CDC. Update: investigation of bioterrorism- related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Mortal Wkly Rep. 2001; 50(42):909-919 CDC. Notice to readers: considerations for distinguishing influenza-like illness from inhalational anthrax. MMWR Morb Mortal Wkly Rep. 2001;50(44):984-986. CDC. Notice to readers: interim guidelines for investigation of and response to Bacillus anthracis exposures. MMWR Morb Mortal Wkly Rep. 2001;50(44):987-990. CDC. Update: interim recommendations for antimicrobial prophylaxis for children and breastfeeding mothers and treatment of children with anthrax. MMWR Morb Mortal Wkly Rep. 2001;50(45):1014-1016. US Department of Health and Human Services. Statement by the Department of Health and Human Services Regarding Additional Options for Preventive Treatment for Those Exposed to Inhalational Anthrax [News Release]. Washington, DC: US Department of Health and Human Services; December 18, 2001. Friedlander AM, Longfield RN. "Anthrax." In: Strickland GT, ed. Hunter’s Tropical Medicine and Emerging Infectious Diseases. Philadelphia, PA: WB Saunders;2000: 384.
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