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Inhalational anthrax: recognizing the symptoms for rapid diagnosis: a flu-like presentation may be an obstacle to diagnosis.

Article Excerpt
ABSTRACT: The 2001 anthrax attack demonstrated the United States' vulnerability to bioterrorism. Governmental and public health agencies are preparing for the enormous logistical challenges required for a response to a large-scale bioterrorist attack. These include the stockpiling and distribution of antibiotics and vaccines for prophylaxis and treatment of exposed populations. Given that untreated inhalational anthrax is rapidly fatal, early identification and timely initiation of appropriate therapy are essential. The prodromal phase of illness is characterized by flu-like symptoms, such as cough, fever, and fatigue, followed by respiratory distress and shock. Chest radiographic findings include pleural effusions and widening of the mediastinum.

KEY WORDS: Anthrax, Bioterrrorism

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The 2001 anthrax outbreak in the United States and the 1979 outbreak in Sverdlovsk, Russia, demonstrated that inhalational anthrax is no longer only of historical interest. (1,2) Unfortunately, the United States is still a possible target for future bioterrorist attacks. The US Commission on National Security, headed by former Senators Rudman and Hart, concluded that the United States is vulnerable to attack and cited biological weapons, such as anthrax, as "the most likely choice and means for disaffected states and groups in the 21st century." (3) There is growing evidence that Al Qaeda is attempting to "produce biological weapons, such as anthrax [to be used] on American soil." (4)

When untreated, inhalational anthrax results in a rapidly fatal illness --usually within 5 days of symptom onset. (5) Thus, it is imperative that health care providers be aware of the clinical signs and symptoms associated with inhalational anthrax, for timely diagnosis and initiation of lifesaving therapy.

In this article, we describe the history of zoonotic, occupational, and bioterrorism-related anthrax exposures. Then, we review the clinical course of inhalational anthrax. In a coming issue of The Journal of Respiratory Diseases, we will review the guidelines for treatment.

BACKGROUND

Microbiology and pathogenesis

The aerobic, gram-positive, non-motile, spore-forming bacterium Bacillus anthracis (size: 1 to 1.5 [micro]m by 3 to 10 [micro]m) causes acute infectious diseases in humans and animals (Figure 1). (6) Viable anthrax spores resist environmental degradation and can exist in the soil for decades. (7) Infection ensues once the spores introduced to the blood and tissue of living hosts germinate into vegetative bacilli.

[FIGURE 1 OMITTED]

The 3 generally accepted routes of B anthracis infection in humans are cutaneous, GI (lower or upper/ pharyngeal), and inhalational. (8) Although several cases of primary anthrax meningioencephalitis have been described, (9) these cases are likely the result of an unrecognized lower respiratory tract (10) or a transethmoidal port of entry. (11-13)

Inhalational anthrax is thought to occur when anthrax particles smaller than 5 [micro]m reach the lower respiratory tract (the alveoli) where alveolar macrophages phagocytize and transport these spores to the hilar and mediastinal lymph nodes. (6,14) The spores germinate and produce bacterial toxins that cause hemorrhage, edema, and necrosis. (15) An initial prodromal syndrome is characterized by flu-like and respiratory symptoms, including fever, cough, and dyspnea. (5,16) A poorly recognized upper airway form of inhalational anthrax, presenting with primarily nonpulmonary symptoms, also has been described. (9)

Inhalational anthrax is not communicable through person-to-person spread from coughing or sneezing. However, there are reported cases of human B anthracis infection spread by contaminated clothing, (17) insect bites, (18, 19) contaminated-needle injection, (20, 21) and by mother-to-child transmission (intrauterine (22-24) or via breast milk (25)).

The primary pathogenesis of B anthracis infection results from the microbe's production of protein toxins rather than from bacterial replication. This is supported by animal studies demonstrating that sterile plasma from anthrax-infected animals is lethal when injected into noninfected hosts. (26)

The virulence determinants of B anthracis are from the bacterial capsule and 2 exotoxins: lethal (composed of lethal factor and protective antigen) and edema toxins. (6) These toxins have several intracellular effects that produce uncontrolled cytokine release, leading to septic shock and respiratory failure from pleural and pulmonary...

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