Fatal Inhalational Anthrax in a 94-Year-Old Connecticut Woman

Barakat, Lydia; Quentzel, Howard; Jernigan, John A.; Kirschke, David; Griffith, Kevin S.; Spear, Stephen M.; Kelley, Katherine A.; Barden, Diane; Mayo, Donald R.; Stephens, David S.; Popović, Tanja; Marston, Chung K.; Zaki, Sherif R.; Guarner, Jeanette; Shieh, Wun‐Ju; Carver, H. Wayne; Meyer, Richard F.; Swerdlow, David L.; Mast, Eric E.; Hadler, James L.

doi:10.1001/jama.287.7.863

Cited by 148 publications

(103 citation statements)

References 14 publications

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“…53,54 The drug rFVIII may enable enhancing coagulation in patients with anthrax who exhibit severe hemorrhage and coagulopathy, as described in clinical settings. [9][10][11][12]31 To develop an effective treatment against anthrax, combining other anti-anthrax agents with a coagulation intervention strategy may be a feasible approach. Figure 6.…”

Section: Discussionmentioning

confidence: 99%

“…6 However, the reason both clinical and animal studies have revealed that hemorrhagic disorder is one of the major manifestations of LT-treated or B. anthracis-infected hosts remains unclear. [7][8][9][10][11][12][13] Recent studies have shown that LT might contribute to hemorrhage by inducing thrombocytopenia and megakaryocytic suppression. [14][15][16] The mechanism underlying coagulation suppression, however, remains undetermined.…”

Section: Introductionmentioning

confidence: 99%

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Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Sun¹,

Lee

Kau

et al. 2015

Virulence

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(2015) Acquired coagulant factor VIII deficiency induced by Bacillus anthracis lethal toxin in mice, Virulence, 6:5, 466-475, DOI: 10.1080/21505594.2015 Keywords: Anthrax, coagulation factor VIII, hemorrhage, lethal toxinMice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. Moreover, LT treatment in mice induced liver damage. In this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. The hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to LT. In agreement with our hypothesis, LT induces cytotoxicity against hepatic cells in vitro. In addition, suppressed expression of coagulation factor VIII (FVIII) in the liver is associated with a prolonged plasma clotting time in LT-treated mice, suggesting a suppressive role of LT in coagulation. Accordingly, we further hypothesized that a loss-of-function approach involving treatments of an anticoagulant should exacerbate LT-induced abnormalities, whereas a gain-offunction approach involving injections of recombinant FVIII to complement the coagulation deficiency should ameliorate the pathogenesis. As expected, a sublethal dose of LT caused mortality in the mice that were non-lethally pretreated with an anticoagulant (warfarin). By contrast, treatments of recombinant FVIII reduced the mortality from a lethal dose of LT in mice. Our results indicated that LT-induced deficiency of FVIII is involved in LT-mediated pathogenesis. Using recombinant FVIII to correct the coagulant defect may enable developing a new strategy to treat anthrax.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Sun¹,

Lee

Kau

et al. 2015

Virulence

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“…The investigation of both inhalational and cutaneous anthrax cases clearly exemplifies these roles. 6,7,60,61 In addition to B. anthracis, several rapid and sensitive IHC assays have been developed for detecting other bioterrorism-related agents, such as Ebola virus, 62,63 Fransicella tularensis, 64 Yersinia pestis, 65 and smallpox virus. These assays provide a method for rapid diagnosis and have fortified the preparedness of responses to possible bioterrorism events.…”

Section: Discussionmentioning

confidence: 99%

The Critical Role of Pathology in the Investigation of Bioterrorism-Related Cutaneous Anthrax

Shieh

Guarner

Paddock

et al. 2003

The American Journal of Pathology

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Cutaneous anthrax is a rare zoonotic disease in the United States. The clinical diagnosis traditionally has been established by conventional microbiological methods, such as culture and gram staining. However, these methods often yield negative results when patients have received antibiotics. During the bioterrorism event of 2001, we applied two novel immunohistochemical assays that can detect Bacillus anthracis antigens in skin biopsy samples even after prolonged antibiotic treatment. These assays provided a highly sensitive and specific method for the diagnosis of cutaneous anthrax, and were critical in the early and rapid diagnosis of 8 of 11 cases of cutaneous anthrax during the outbreak investigation. Skin biopsies were obtained from 10 of these 11 cases, and histopathological findings included various degrees of ulceration, hemorrhage, edema, coagulative necrosis, perivascular inflammation, and vasculitis. Serology was also an important investigation tool, but the results required several weeks because of the need to test paired serum specimens. Other tests, including culture, special stains, and polymerase chain reaction assay, were less valuable in the diagnosis and epidemiological investigation of these cutaneous anthrax cases. This report underscores the critical role of pathology in investigating potential bioterrorism events and in guiding epidemiological studies, Anthrax captured worldwide attention and aroused serious public health concerns following the intentional release of the etiological agent Bacillus anthracis in the United States postal system during Fall 2001, 1,2 resulting in 11 cases of inhalational anthrax and 11 cases of cutaneous anthrax. [3][4][5][6][7] In its conventional form, cutaneous anthrax accounts for 95% of all naturally occurring B. anthracis infections in the United States. 8 -11 Patients often have a history of occupational contact with animals or animal products contaminated with B. anthracis spores. 12-14 These pathogenic spores are introduced through a cutaneous cut or abrasion, with the most common areas of exposure are the head, neck, and extremities, although any area can be involved. Bacteremia and toxemia following cutaneous infection can occur with a fatality rate of 20% to 25% among untreated cases. [15][16][17] Cutaneous anthrax is characterized by the formation of a black eschar surrounded by prominent edema and vesicles, which may resemble many other skin lesions, such as the brown recluse spider bite, 18 -21 ulceroglandular tularemia, 22,23 plague, 24,25 ecthyma gangrenosum, 26,27 various spotted fever group rickettsial infections, 28 -31 and scrub typhus. 32,33 The clinical diagnosis of cutaneous anthrax is traditionally established by microbiological methods (eg, demonstrating gram-positive, capsulated bacilli on the smear of the lesion or isolating B. anthracis in culture). 34,35 However, gram stain and culture for B. anthracis can be unrevealing for patients who receive antibiotic therapy before specimens are obtained. 36,37 Historically, skin biopsies ...

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“…Fulminant victims receiving critical care would be rescued based on the survival rate (58.3%) of recent inhalational anthrax cases. [36][37][38] Rescued ICU victims would then receive 10 days of non-ICU inpatient care.…”

Section: Kyriacou Et Almentioning

confidence: 99%

Cost-Effectiveness Comparison of Response Strategies to a Large-Scale Anthrax Attack on the Chicago Metropolitan Area: Impact of Timing and Surge Capacity

Kyriacou

Dobrez

Parada

et al. 2012

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, an

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Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. However, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. We conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the Chicago metropolitan area beginning either Day 2 or Day 5 after the attack. ICU bed availability significantly reduces mortality for all response strategies. We conclude that postattack antibiotic prophylaxis and vaccination of all exposed people is the optimal cost-effective response strategy for a large-scale anthrax attack. Our findings support the US government's plan to provide antibiotic prophylaxis and vaccination for all exposed people within 48 hours of the recognition of a large-scale anthrax attack. Future policies should consider expanding critical care capacity to allow for the rescue of more victims.

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Fatal Inhalational Anthrax in a 94-Year-Old Connecticut Woman

Cited by 148 publications

References 14 publications

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

The Critical Role of Pathology in the Investigation of Bioterrorism-Related Cutaneous Anthrax

Cost-Effectiveness Comparison of Response Strategies to a Large-Scale Anthrax Attack on the Chicago Metropolitan Area: Impact of Timing and Surge Capacity

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