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Abstracts & Commentary
Synopsis: The initial symptoms of inhalational anthrax are similar to those of influenza and other viral respiratory tract infections. Since no rapid diagnostic test is available for early anthrax, the use of rapid viral diagnostics assumes great importance.
Sources: CDC. MMWR Morb Mortal Wkly Rep. 2001;50:941-948; Jernigan JA, et al. Posted Nov. 8, 2001. www.cdc.gov/ncidod/EID/index.htm.
The CDC has reviewed the first 16 confirmed (see Table) and 5 suspected cases of bioterrorism-related anthrax occurring in the United States since October 3, 2001, and has made suggestions for the clinical evaluation and diagnostic testing of individuals who may have this disease.
|Table: Anthrax: Operational Definitions|
|CDC defines a confirmed case of anthrax as: 1) a clinically compatible case of cutaneous, inhalational, or gastrointestinal illness that is laboratory confirmed by isolation of B anthracis from an affected tissue or site or 2) other laboratory evidence of B anthracis infection based on at least 2 supportive laboratory tests.|
|CDC defines a suspect case as: 1) a clinically compatible case of illness without isolation of B anthracis and no alternative diagnosis, but with laboratory evidence of B anthracis by 1 supportive laboratory test or 2) a clinically compatible case of anthrax epidemiologically linked to a confirmed environmental exposure, but without corroborative laboratory evidence of B anthracis infection.|
|For more information see: www.bt.cdc.gov/Agent/Anthrax/Anthrax.asp|
The 10 patients with inhalational anthrax, 7 of whom were men, ranged in age from 43 to 73 years. The incubation period in the 7 patients for whom the date of exposure was known ranged from 5 to 11 days (median, 7 days). The onset of illness was associated with fever in 9 and/or sweats with or without chills in 6. Nine had nonproductive cough and 1 of these had blood-tinged sputum. Eight had chest discomfort or pleuritic pain while 5 reported "chest heaviness;" 7 had shortness of breath. Five had abdominal pain, nausea, or vomiting. Other symptoms included severe fatigue or malaise, headache, myalgias and, in 2 patients, sore throat. One patient had rhinorrhea.
The initial white blood cell (WBC) count in these 10 patients with inhalational disease ranged from 7500/mm3 to 13,300/mm3, often with a "left shift." Abnormalities were present on the chest x-ray of all 10; 7 of 8 who had a chest CT had mediastinal widening and/or hilar enlargement, although evidence of mediastinal widening on plain radiograph was absent or had been subtle in some. Seven patients had pleural effusions that were often large and hemorrhagic; in 2 of these 7, no mediastinal widening was seen on chest x-ray. Four of the 10 had pulmonary infiltrates and these involved more than 1 lobe in 3 of the 4. One patient had meningitis.
Bacillus anthracis grew from blood cultures of 7 patients, including all who had not received antibiotics prior to obtaining the specimen. The diagnosis in patients with negative blood or pleural fluid cultures was made by immunohistochemical staining of bronchial or pleural biopsy specimens, by PCR of fluids, or by a 4-fold increase in IgG antibody to protective antigen (PA). Six of the 10 patients, including all who received antibiotics during the initial prodromal phase of the illness, survived.
The estimated incubation period in the 11 patients with cutaneous anthrax ranged from 1 day to 10 days (mean, 5 days). The patients complained of tingling sensation or pruritus, but not pain, at the site of the lesion. The diagnosis was made in some cases when only an erythematous papule was present.
No cases of anthrax have occurred in individuals who had started prescribed antibiotic prophylaxis prior to the onset of symptoms.
Comment by Stan Deresinski, MD, FACP
As we approach the winter season, we are likely to be faced with increasing numbers of patients with influenza-like illnesses who are fearful that they may have inhalational anthrax. This will present a difficult problem in clinical management. The algorithms from the CDC publication provide some help in this regard (see Figure 1 and Figure 2).
As can be seen, however, the initial symptoms of inhalational anthrax are extremely similar to those of influenza and many other respiratory tract infections. Thus, a recent analysis of a large number of patients with laboratory-documented influenza found that the most frequently reported symptoms, occurring in at least 90%, were weakness, myalgia, cough, and nasal congestion, feverishness, anorexia, and headache.1 Sore throat was reported by 84%. These symptoms were as common or almost as common in patients in the study who were not found to have influenza virus infection. A comparison of symptom lists suggests to me that the only potential differentiating feature may be the absence of nasal congestion as a common complaint in inhalational anthrax.
The similarity of symptoms in inhalational anthrax and viral respiratory tract infection, especially influenza, together with the absence of a rapid diagnostic test for early inhalational anthrax (although 1 from Roche Labs and the Mayo Clinic may be available soon), makes the task for the clinician exceedingly difficult. A useful approach may be the use of rapid diagnostic tests for viral respiratory tract infection in patients presenting with compatible symptoms.
A number of rapid tests are available for the diagnosis of influenza virus infection. In a direct comparison, with influenza culture and DFA testing as the comparison, 3 rapid diagnostic tests—Flu OIATM, Quickvue Influenza TestTM, and Directigen FluTM—were essentially equivalent, with sensitivities of 82-88% and specificities of 93-96%. A fourth test, Z Stat FluTM, had comparable sensitivity, but its specificity was only 73%.2 These immunoassays require 10 to 20 minutes for completion and have similar costs. A number of tests are also available for rapid diagnosis of other viral infections, including RSV and parainfluenza virus infections. A multiplex PCR assay, HexaplexTM, under review by the FDA, detects RSV A and B, influenza A and B, and parainfluenza 1-3, but requires approximately 8 hours to perform. The test is under FDA review.
1. Monto AS, et al. Arch Intern Med. 2000;160: 3242-3247.
2. Infectious Diseases Society of America Annual Meeting. San Francisco, Calif., Oct. 25-28, 2001. Abstract #604.
Dr. Deresinski, Clinical Professor of Medicine, Stanford; Director, AIDS Community Research Consortium; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert.