Larry M. Bush, MD; Maria T. Perez, MD
Ten years ago, just weeks after the September 11 attacks, the United States experienced a deliberate act of bioterrorism. Through use of the postal service, anthrax spores were widely disseminated, including to homes, the Senate, and major newsrooms, resulting in morbidity and mortality and effectively disrupting our way of life and revealing our vulnerability. Even though such attacks had been the subject of much writing and had been planned for, detection of and the appropriate response to an attack with an agent from the so-called “Category ‘A’ List” had only been considered in theoretical terms. What transpired during the following difficult weeks, including how public health and federal government agencies performed, has been both praised and criticized. An intertwined epidemiologic and criminal investigation of such magnitude was unprecedented in U.S. history. To address the question of whether we as a nation are now better prepared for future threats involving biologic agents, it is important to learn from the lessons of the 2001 anthrax attacks, including the critical role of clinicians in surveillance. As physicians involved in diagnosing anthrax in the index case and alerting authorities, we offer our perspective on these events a decade after their occurrence.
Large, boxcar-shaped, gram-positive bacilli and polymorphonuclear leukocytes (Gram stain; original magnification, ×400).
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Professor Faculty of Human Medicine National University of San Marcos
October 30, 2011
EARLY DIAGNOSIS OF CUTANEOUS ANTHRAX: A KEY ELEMENT IN BIOTERRORISM
In the article: The Anthrax Attacks 10 Years Later, the authors teach it is important to learn from the lessons of the 2001 anthrax attacks, including the critical role of clinicians in surveillance (1) but they don't mention cutaneous anthrax. Inhalation anthrax is the main clinical form in the bioterrorism scope given its high mortality, however early diagnosis (a time when treatment can be effective) (2), is rather difficult to achieve. Although the cutaneous form has low mortality rates and is thus, considered as less important in a bioterrorist attack, its diagnosis may serve as an epidemiological alert and lead, indirectly, to the early search for possible inhalation anthrax cases. Because of this, it is necessary for physicians to learn to recognize cutaneous anthrax at its early stage. Contrary to what occurs with the inhalation form, cutaneous anthrax has well defined clinical characteristics and is relatively easy to diagnose clinically, however, the early stage of cutaneous anthrax often remains undiagnosed, probably due to many reasons: a) It is a rare pathology; b) The physician associates this pathology mainly with a late- stage necrotic ulcer and; c) Absence of pain in the cutaneous lesion makes the patient recognize the cutaneous lesion late and delay seeking medical attention. These difficulties in early recognition were observed in the bioterrorism event with anthrax in the United States. In this epidemic, the first cases were not inhalation, but cutaneous (3). These first seven cutaneous cases were not diagnosed until the eighth patient died of inhalation anthrax. An infant was hospitalized with a cutaneous anthrax lesion at an early stage without being recognized as such. Even when the lesion progressed to a necrotic ulcer in the late stage, this lesion was wrongly diagnosed as loxoscelism. The infant went on to develop hemolytic anemia and required management in the intensive care unit (4). Although the patient was taken to the hospital early and high technology testing, such as PCR or nuclear MRI, was conducted, the main, most accessible and economic test, that is the clinical diagnosis, was done inadequately. Emphasis on early clinical recognition of cutaneous anthrax is highly used in anthrax endemic areas in Peru, as part of the traditional medicine knowledge developed by these communities due to the absence of physicians and it could be useful to the field of bioterrorism (5).
1. Bush L. Perez M .The Anthrax Attacks 10 Years Later Ann Intern Med. 2011 Oct 3 (Epub ahead of print)
2. Mc Carthy M. Early and aggressive treatment saves US antrax victims. Lancet. 2001 ; 358 : 1703
3. Gursky E, Inglesby T, O Toole T. Anthrax 2001: observations on the medical and public health response.Biosecur Bioterror. 2003;1 : 99.
4. Freedman A, Afonja O, Chang MW. et al. Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7- month-old infant. JAMA. 2002; 287: 869-74.
5. Salinas -Flores D. Diagnostico y Tratamiento del Antrax: Medicina Tradicional vs. Medicina Cientifica. Rev Per Enf Inf Trop. 2001;1:157- 164
William B.Baine, Senior Medical Advisor
Agency for Healthcare Research and Quality
January 21, 2012
Anthrax, Bioterrorism, and CLIA
Postal anthrax highlights a neglected diagnostic issue (1). When Dr. Bush looked through the microscope at the Gram-stained smear of cerebrospinal fluid and nailed the diagnosis, did he not violate CLIA, the Clinical Laboratory Improvement Amendments of 1988 (2)? The Centers for Medicare and Medicaid Services (CMS) require diagnostic laboratories to demonstrate proficiency in the tests they perform. The definition of "laboratory" is straightforward in the legislation (3), but the CLIA Internet site overreaches: "CLIA requires all entities that perform even one test...to meet certain Federal requirements. If an entity performs tests for these purposes, it is considered under CLIA to be a laboratory and must register....(2)." A look at his patient's Gram stain transforms Dr. Bush into a laboratory "entity," even if he does not bill for the microscopy.
The biennial certification fee for a laboratory with an Annual Test Volume of 2,000 or fewer is $150 (2). The Medical Laboratory Evaluation Program offers a CLIA-approved Gram stain proficiency test for $156 (4). These are the costs of doing business if you operate a real office laboratory with its own revenue stream. How many other clinicians budget $306 for a two-year option of the occasional uncompensated Gram stain when working up a sick patient?
How grave was the problem before 1988 of incompetent Gram-stainers' running riot? Crystal violet is not crystal meth: Paine bemoaned "a perpetual disinclination for doing gram stains in situations in which the procedure would be helpful" (5). Should Dr. Bush's patients be thankful for the $306 disincentive to his sitting down at one of the microscopes in the hospital lab before rendering an opinion? If patients benefit when clinicians must pay to prove proficiency before they can choose whether to use microscopes, how about statutes restricting ophthalmoscopes, otoscopes, and stethoscopes?
What would Paine make now of a $6.42 billion fiscal 2012 civilian biodefense budget (1) when the only detector that has actually been shown to work--"an astute clinician" (1) looking into a microscope--risks fines or imprisonment if "convicted of intentionally violating any CLIA requirement" (3)?
CLIA needs one more amendment--a general exemption for any direct specimen examination by microscopy by a physician as an integral part of a patient evaluation without separate or supplemental billing.
Oh, yes, Dr. Bush was right about one more thing--the smear was underdecolorized. Leukocytes with purple nuclei belong on Wright-stained slides. Here the nuclei should have been pink.
1. Bush LM, Perez MT. The anthrax attacks 10 years later. Ann Intern Med 2012;156:41-4.
2. https://www.cms.gov/clia/ on 19 January 2012.
3. Definitions, 42 C.F.R. Sect. 493.2 (2004).
4. http://www.acponline.org/running_practice/ mle/catalog/2012/catalog.pdf on 19 January 2012.
5. Paine TF Jr. Gram staining without the clock. N Engl J Med 1963;268:941.
The opinions in this comment are those of the author, who is responsible for its content, and do not necessarily represent the views of the Agency for Healthcare Research and Quality (AHRQ). No statement in this comment should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
Larry M. Bush, Maria T. Perez. The Anthrax Attacks 10 Years Later. Ann Intern Med. 2012;156:41–44. doi: 10.7326/0003-4819-155-12-201112200-00373
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Published: Ann Intern Med. 2012;156(1_Part_1):41-44.
Bioterrorism Infectious Agents, Infectious Disease.
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