Second and Subsequent Infection of Anthrax Again After Recovery
Am J Respir Crit Care Med. 2011 Dec 15; 184(12): 1333–1341.
Anthrax Infection
Daniel A. Sweeney
aneMedical Intensivist Plan, Washington Hospital, Fremont, California
Caitlin W. Hicks
2Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio; and
Xizhong Cui
3Critical Care Medicine Department, Clinical Heart, National Institutes of Health, Bethesda, Maryland
Yan Li
3Critical Care Medicine Section, Clinical Heart, National Institutes of Health, Bethesda, Maryland
Peter Q. Eichacker
threeCritical Intendance Medicine Department, Clinical Center, National Institutes of Wellness, Bethesda, Maryland
Received 2011 Feb 2; Accustomed 2011 Jul 8.
- Supplementary Materials
-
Disclosures
GUID: 8C1A7055-C7B1-4167-9FBF-96291ADC95BA
GUID: 59D685F6-CDA3-4E3B-A681-BBBCB46699D6
Other Clinical Reviews
GUID: 7A666362-100B-4042-800F-A5B74F726CD1
Abstruse
Bacillus anthracis infection is rare in developed countries. However, recent outbreaks in the Us and Europe and the potential utilize of the bacteria for bioterrorism accept focused interest on it. Furthermore, although anthrax was known to typically occur equally one of three syndromes related to entry site of (i.e., cutaneous, gastrointestinal, or inhalational), a quaternary syndrome including severe soft tissue infection in injectional drug users is emerging. Although shock has been described with cutaneous anthrax, information technology appears much more common with gastrointestinal, inhalational (5 of 11 patients in the 2001 outbreak in the United States), and injectional anthrax. Based in part on instance series, the estimated mortalities of cutaneous, gastrointestinal, inhalational, and injectional anthrax are 1%, 25 to 60%, 46%, and 33%, respectively. Nonspecific early on symptomatology makes initial identification of anthrax cases difficult. Clues to anthrax infection include history of exposure to herbivore animal products, heroin utilize, or clustering of patients with like respiratory symptoms concerning for a bioterrorist upshot. Once anthrax is suspected, the diagnosis can ordinarily be made with Gram stain and civilisation from blood or surgical specimens followed by confirmatory testing (east.yard., PCR or immunohistochemistry). Although antibiotic therapy (largely quinolone-based) is the mainstay of anthrax handling, the use of adjunctive therapies such as anthrax toxin antagonists is a consideration.
Keywords: Bacillus anthracis, diagnosis, pathogenesis, handling
Until recently, Bacillus anthracis (anthrax) infections were relatively infrequent and confined to agrarian communities in underdeveloped countries. All the same, the 2001 bioterrorism assail in the United states of america and the outbreak of anthrax infections amongst injectional drug users in Europe in 2009 and 2010 demonstrate that the clinical relevance of anthrax has greatly increased. Anthrax has been classified into one of iii syndromes based on the principal site of infection: cutaneous, gastrointestinal, or inhalational. A 4th syndrome, characterized by severe soft tissue infections in injection drug users, has emerged. Because of the depression incidence of anthrax in developed areas and the nonspecific early symptoms, many patients in these outbreaks have presented with avant-garde infection, which has progressed rapidly to stupor. The morbidity and mortality in such patients has been high. This review discusses the microbiology of B. anthracis, key features of the differing syndromes, the features and potential mechanisms underlying stupor with anthrax, and the diagnosis and treatment of anthrax.
Microbiology
B. anthracis is a gram-positive, rod-shaped bacteria that exists in the environment equally a spore and can remain viable in the soil for decades (ane). Spores ingested past grazing herbivores germinate within the animal to produce the virulent vegetative forms that replicate and eventually kill the host. Products (e.g., meat or hides) from infected animals serve as a reservoir for human being disease. Germination from spore to vegetative organism is thought to occur inside host macrophages and is mediated past specific interactions betwixt nutrients (primarily amino acids and purine nucleosides) and germinant nutrient receptors located on the inner membrane of the spore (2). Physiologic body temperature, as well as blood and tissue carbon dioxide levels, contribute to this process past triggering the production of of import virulence factors (3). The relative ease with which large amounts of B. anthracis tin be grown under laboratory conditions and the spore'south resistance to killing and ease of dissemination facilitates the potential utilize of the microbe for bioterrorism (four).
Later germination occurs, 3 factors appear key to the pathogenesis of anthrax: a sheathing, the production of two toxins (i.e., lethal and edema), and the bacteria's ability to achieve loftier concentrations in infected hosts (5). Virulent anthrax strains carry two plasmids, pXO1 and pXO2, which encode the capsule and toxin components. The plasmids are regulated by the transcriptional factor AtxA, which is modulated by environmental factors (6). The capsule resists phagocytosis and is weakly immunogenic. Lethal toxin (LT) and edema toxin (ET) are binary toxins, each made up of two proteins: protective antigen (PA) and lethal factor (LF) for LT and PA and edema cistron (EF) for ET. Protective antigen mediates jail cell binding and uptake of LF and EF, the toxigenic components. Lethal factor is a zinc metalloprotease that selectively inactivates mitogen-activated protein kinase kinases 1 to 4 and 6 and 7 (7). Edema factor is a calmodulin-dependent adenyl cyclase that increases intracellular campsite levels to very high levels (viii). Moayeri and Leppla provide an excellent overview of the potential deportment of LF and EF in a contempo review (9).
During infection, circulating PA binds to one of at least ii host cellular receptors, tumor endothelial mark eight or capillary morphogenesis cistron two, present on many tissues (Figure 1) (10). The bound PA precursor molecule undergoes furin cleavage with release of an unbound subunit. Bound PA subunits form a heptamer that one to iii circulating LF and EF proteins competitively demark to. This complex undergoes endocytosis, and the toxic factors are released intracellularly.
Key events in the uptake of edema or lethal toxin past host cells as well as the potential effects of edema and lethal cistron. During infection, circulating protective antigen (PA) binds to 1 of at least two host cellular receptors, anthrax tumor receptor (ATR) encoded past the tumor endothelial marker viii gene or another receptor encoded by the capillary morphogenesis gene two (CMG2), both of which are present on many tissues. The bound PA precursor molecule undergoes furin cleavage with release of an unbound subunit. Jump PA subunits form a heptamer that one to three circulating lethal factor (LF) or edema cistron (EF) proteins competitively demark to. This complex undergoes endocytosis, and the toxic factors are so released into the cytoplasm. Edema factor has calmodulin-dependent adenyl cyclase activeness and increases intracellular campsite levels, whereas LF inhibits mitogen activated protein kinase kinase 1 to 4, 6, and seven. These factors have been shown to influence the function of several different types of host cells, every bit summarized by Moayeri and Leppla (9).
Anthrax Clinical Syndromes
Cutaneous Anthrax
Ninety-five percentage of reported anthrax cases are cutaneous, and most occur in Africa, Asia, and Eastern Europe where animal and worker vaccination is limited (xi). It is estimated that there are approximately 2,000 cases annually worldwide (12). In the 2001 anthrax outbreak in the Usa, cutaneous anthrax accounted for 11 of 22 cases (13). Cutaneous anthrax frequently resolves spontaneously, with the bloodshed rate for untreated infections estimated to be between 5 and xx% (1). With appropriate antibiotic handling, the mortality charge per unit is less than 1% (fourteen). Still, cutaneous anthrax tin can produce daze, with one recent case series reporting an incidence of 9% (ii of 22 patients diagnosed with cutaneous anthrax) (15).
Cutaneous anthrax results when spores are introduced via breaks in exposed pare areas. The spores germinate inside macrophages locally or in regional lymph nodes, and vegetative forms are released (1). The incubation period is from 1 to 12 days (one, 14). The initial peel lesion is a painless or pruritic papule associated with a disproportionate amount of edema and which progresses to a vesicular form (1–ii cm). Fever and regional lymphadenopathy can occur. The vesicle and then ruptures and forms an ulcer and black eschar, which sloughs in 2 to 3 weeks (11, 14) (Effigy ii). Purulence is only seen with secondary nonanthrax infection. Edema with face or cervix infection may produce airway compromise (12).
Cutaneous anthrax. These lesions appeared on the arms of a man who 6 days earlier had handled ill cattle. The extensive edema and hemorrhagic vesicles and bullae are typical of cutaneous anthrax and announced earlier the formation of a black eschar (15).
Gastrointestinal Anthrax
Gastrointestinal anthrax is typically related to ingestion of spore-contaminated meat. Although gastrointestinal anthrax is uncommon, its incidence may exist underestimated due to the infection's nonspecific symptomatology. The mortality rate is estimated to exist 25 to 60%, and, although the rate of associated shock is not known, case reports note that severe cases are frequently complicated past shock (sixteen, 17). The only confirmed case of gastrointestinal anthrax in the United States was atypical in that it occurred in a person who likely swallowed aerosolized anthrax spores released from an animal-hibernate pulsate (18, 19). This patient'due south clinical form was complicated past shock.
There are two forms of gastrointestinal anthrax: oropharyngeal and intestinal. In oropharyngeal anthrax, spores settle in the pharyngeal surface area and produce ulcers. In the largest outbreak reported in 24 persons from Thailand who ate contaminated beef, the mean incubation time was 42 hours (xx). Nigh patients presented with fever and neck swelling secondary to cervical lymphadenopathy. Initial ulcers were associated with congestion, followed past primal necrosis, whitish discoloration, and somewhen a pseudomembranous roofing. In intestinal anthrax, spores deposit and cause ulcerative lesions anywhere from the jejunum to the cecum. The ulcers are associated with mesenteric lymphadenopathy and ascites and can lead to intestinal obstruction, bleeding, and perforation (20). Patients oft present with nonspecific gastrointestinal symptoms (i.e., nausea, vomiting, abdominal pain, or diarrhea). In more severe cases, fever, ascites, increased intestinal girth, and shock develop (17).
In the one confirmed instance in the United States, the patient initially experienced influenza-like symptoms followed past nausea, vomiting, and abdominal cramps (18, 19). The patient then developed hypotension. Laboratory information were notable for leukocytosis, hemoconcentration, and an abdominal CT showing massive ascites, thickened small bowel segments, and prominent retroperitoneal lymphadenopathy (Figure three). Exploratory laparotomy showed nodular hemorrhagic lesions in the mesentery and two areas of necrotic modest bowel. The modest bowel lesions and the appendix were resected. Hypotension and respiratory failure subsequently worsened. Repeat laparotomy showed a retroperitoneal hematoma that was removed. Besides antibiotics and other supportive measures, this patient received antiimmune globulin (AIG; Cangene, Winnipeg, MB, Canada). Afterward the second surgical procedure, the patient recovered.
Gastrointestinal anthrax. Coronal reconstruction images from a CT scan of the abdomen and pelvis later on the administration of intravenous contrast material prove a large amount of ascites and concentric wall thickening of a long segment of the distal small bowel (A, arrows). Numerous slightly enlarged lymph nodes are enhanced with intravenous contrast material and are seen at the root of the minor bowel mesentery (A, arrowheads) and in the retroperitoneum (B, arrowheads) (19).
Inhalational Anthrax
During the 19th century, inhalational anthrax occurred in the United States and Europe amid millworkers handling spore-contaminated animal hides. Industrial outbreaks are now rare due to animal vaccination, disinfecting processes, and improved mill ventilation (21, 22). Nonetheless, sporadic cases occur, peculiarly among artisans working with animal products from owned areas (23–25). Bioterrorism remains the greatest risk for a large-calibration outbreak, equally evidenced by the adventitious release of weapons-grade anthrax in Sverdlovsk, Russia in 1979 and the 2001 outbreak in the United States (26). The mortality rate appears to take improved over fourth dimension: 94% in naturally occurring cases earlier 1976, 86% in Sverdlovsk, and 46% in the outbreak in the United states (26, 27). Improved survival has been attributed to before diagnosis, improve supportive intendance, and early on and multidrug antibiotic therapy (i, 28).
Inhalational anthrax is acquired by inhalation and alveolar degradation of spores less than five μm in size (1). Spores are phagocytosed past macrophages and carried to local mediastinal lymph nodes where they germinate into vegetative forms, replicate, and produce hemorrhagic mediastinitis (26, 29). If ineffectively treated, bacteremia and toxemia ensue, resulting in meningitis, gastrointestinal interest, and refractory daze. Although inhalational anthrax is more often than not not considered an airspace disease, histology at autopsy sometimes shows focal pneumonia, perhaps representing the initial site of microbial entry (26).
Inhalational anthrax has a biphasic clinical course (21, 28). After an incubation menses of approximately four days, patients develop flu-like symptoms with fever, nonproductive cough, and myalgias lasting approximately 4 days. Without timely treatment, a 2nd fulminant stage follows, characterized past hypotension and dyspnea. This phase may progress to death within 24 hours of its onset (21). A systematic review of 82 inhalational anthrax cases in the U.s. from 1900 to 2001 noted common access findings in patients who lived (n = 12) or died (n = 70) (21, 28). Although not reported for all patients, the most frequent findings were fever or chills (92 and 62% in patients who lived or died), coughing (100 and 54%), dyspnea (83 and 46%), fatigue or angst (75 and 62%), aberrant torso temperature (92 and 78%), lung findings on physical examination (100 and 74%), and tachycardia (83 and 61%). Chest radiography was consistently aberrant, most notably showing pleural effusions or a widened mediastinum in 100% of patients whether they lived or died (Figure 4). An elevated hematocrit has also been noted with inhalational anthrax. This finding, along with a widened mediastinum on radiograph and contradistinct mental status, may help differentiate it from community-acquired pneumonia (27). A retrospective analysis of inhalational anthrax and community-acquired pneumonia cases calculated that a derived algorithm based on these three variables was 100% sensitive (95% confidence interval, 73.5–100) and 98.3% specific (95% confidence interval, 95.i–99.half-dozen) for differentiating the ii weather condition.
Inhalational anthrax. (A and B) The contrast-enhanced chest CT scans from a patient with inhalational anthrax shows perihilar parenchymal lung disease (A, arrow), widening mediastinum, hilar adenopathy, pleural effusions, and peribronchial infiltrates every bit well as patchy peribronchial air-infinite disease, especially on the correct (B, arrow). (C–Eastward) Photomicrographs of histopathologic specimens of hilar soft tissue from the same patient at dissection shows perivascular and peribronchial hemorrhage (C, arrow; H&Due east; original magnification: ×10), hemorrhage and necrosis (D, pointer; H&East; original magnification: ×20), and abundant gram-positive bacilli (E, arrow; Brown-Brenn; original magnification: ×100) (84).
Antibiotic treatment chop-chop sterilizes blood cultures with inhalational anthrax and progressive disease, and death in severely ill patients in the fulminant stage of disease has been postulated to be due ongoing toxin release (25). Nonetheless, assays capable of measuring anthrax toxin components have not been sufficiently practical in conjunction with culture testing to ostend this possibility.
Injectional Anthrax
In 2001, a heroin user in Norway developed an anthrax soft tissue infection resulting from a subcutaneous drug injection. Infection was complicated by septic stupor, meningitis, and expiry despite therapy. This syndrome, which appeared different from cutaneous disease, was referred to equally "injectional anthrax" (xxx). A major outbreak of injectional anthrax has recently occurred in the United Kingdom (47 recognized cases and 13 deaths in Scotland, v cases and 4 deaths in England) primarily in subcutaneous or intramuscular heroin users (31, 32). Ii cases (and one death) have been noted in Germany (33, 34). Important differences between cutaneous and injectional anthrax have included an increased take a chance of shock and a higher mortality rate despite antibiotic therapy (< i% versus 34%, respectively). There were several potential sources for contamination of this heroin. Almost heroin sold in Europe originates in Afghanistan and is transported through Iran and Turkey—all countries where anthrax is enzootic (35, 36). Moreover, heroin is routinely cutting by 50 to 99% with diluents before and afterwards it reaches the consumer. It is estimated that 61 to 68% of street heroin samples in the The states are contaminated with pathogens, most frequently nonanthrax Bacillus species (37).
Information technology is believed that in injectional anthrax, spores germinate at the inoculation site, and the leaner'due south capsule facilitates local spread. Whether disseminated illness results from intravascular injection of spores or spread of local soft tissue infection is unknown. Significant edema at the injection site is common, just, in dissimilarity to cutaneous affliction, papules, vesicles, and eschars are not typically observed (thirty, 38) (Figure five). Excessive bruising at the injection site may occur early. Such symptoms are common in intravenous drug users. Differences in these early symptoms and the impetus to seek medical attention comparison cutaneous and injectional anthrax may provide a footing for the poorer observed prognosis with the latter. Alternatively, injectional anthrax may involve the delivery of a larger and more concentrated bacterial inoculum to a deeper site. Surgical exploration of wounds from injectional anthrax cases has revealed prominent tissue edema, diffuse capillary bleeding, and necrosis of the superficial adipose tissue. These lesions differed from abscesses that contain purulent material and from necrotizing fasciitis, which involves deeper soft tissue and is characterized past microvascular thrombosis and turbid fluid (38). Severe cases developed thrombocytopenia and coagulopathy. After initial hemodynamic stabilization, a notable number of patients accept developed recurrent daze resistant to therapy.
Injectional anthrax. Preoperative photographs of a woman (A) with peel necrosis involving the medial aspect of her left thigh and labia majora and a man (B) with swelling of his scrotum and skin necrosis involving his buttock (85). (C) Surgical debridement of necrotic pare and fascia of a patient with injectional anthrax and compartment syndrome of the right arm (76).
Stupor During Anthrax Infection
Clinical Characteristics
Although shock is rare with cutaneous anthrax, it occurs commonly with inhalational disease (five/11 cases in the 2001 outbreak in the Usa) (13, 39). The rates of shock associated with gastrointestinal or injectional anthrax are non well defined but also announced substantial (20, 38). The recent confirmed example of gastrointestinal anthrax in the U.s.a. adult astringent stupor. In preliminary reports from the experience with injectional anthrax in the United Kingdom, stupor was also a notable finding. There are few invasive systemic or myocardial hemodynamic measures bachelor clinically to help characterize the pathophysiologic mechanisms underlying anthrax-associated daze. For instance, to what extent peripheral vascular versus myocardial dysfunction contributes is unknown clinically. Still, at that place are a number of unique clinical features that have been noted. Although hemoconcentration is rare in sepsis due to more than common pathogens, it has been frequently noted with anthrax-associated sepsis (xv, xix, 27). This finding is likely related in part to fluid shifts. Soft tissue edema is a hallmark of cutaneous anthrax and can extend well beyond the site of infection. Likewise, fluid collections in the chest or abdomen are typical of inhalational and gastrointestinal anthrax, respectively. The fact that liberal fluid resuscitation (> 10 L in 24 h) and extensive soft tissue edema accept been described with injectional anthrax locally and in areas distant from the infection site suggests that extravasation of fluid as well occurs with this syndrome (38). Hyponatremia has too been a frequent finding in inhalational anthrax and was described in 8 of 10 cases in the 2001 outbreak in the Usa (40). How often this occurred before every bit opposed to after fluid resuscitation is not known.
Another notable difference from other types of bacteria is that once anthrax infection progresses to septic shock, it appears to be very resistant to conventional supportive measures (38). In the 2001 outbreak in the United States, the five patients reported to develop hemodynamic instability died despite aggressive support. The mortality rate, specifically in patients with shock in the injectional anthrax outbreak in the United Kingdom, has non been reported. Because some of the patients did not require ICU care, the overall number of deaths described (18/53) suggests a high mortality rate among those patients who required intensive intendance therapies.
Potential Pathogenic Mediators
Although clinical observations are limited, preclinical studies provide insight into potential mechanisms underlying daze during anthrax. Several bacterial components may contribute to this. Even so, how the actions of these components interact is unclear.
Lethal toxin.
In vivo studies since the outbreak in the United States take shown that LT may play an important office in shock during anthrax infection and that its mechanisms of action are probable multifactorial. In rats, 24-hour LT infusions simulating toxin release during infection produced progressive hypotension, hemoconcentration, and increased lactate (41). Like LT infusions in sedated, instrumented, and mechanically ventilated canines acquired progressive shock associated with reductions in primal venous pressure that persisted in nonsurvivors and were associated with lactic acidosis (42). These and other findings take suggested that LT may alter peripheral vasculature role. Consistent with this, in vitro LT disrupts endothelial jail cell role through stimulation of endothelial cell apoptosis and alterations in actin fibers and via mast prison cell activation (10, 43–45). Pulmonary dysfunction has not been prominent in these LT-challenged models. However, LT may also directly depress myocardial function. LT injection in rats and a limited number of canines reduced left ventricular role when measured 18 or 96 hours later, respectively (46). In mice, LT challenge reduced left ventricular ejection fraction (LVEF) every bit early as 6 hours (9). In some other canine model, 24-hour LT infusions caused progressive reductions in LVEF from 48 to 96 hours but not in pulmonary avenue apoplexy pressures (42). Consistent with these in vivo findings, LT depressed cardiac myocyte function in vitro via NADPH oxidase-mediated mechanisms (47). Finally, it is possible that LT has a direct result on mitochondrial or other function that injures cells. In rats, a regimen of norepinephrine infusion, which improved survival in LPS-challenged animals, increased blood pressure but not survival with LT (48).
Edema toxin.
Although on a molar weight basis ET is less lethal than LT, it may play an important part in shock with anthrax. Clinically, substantial extravasation of fluid with astringent anthrax cases has implicated ET in systemic infection (thirteen). EF is known to increase intracellular army camp to very high levels (8). cAMP in turn plays a primal function in stimulating vasodilation (49, 50). In canines, 24-hr ET infusions apace reduced key venous arterial and blood pressure in patterns persisting for up to 96 hours (42). These changes were not associated with hemoconcentration or extravasation of fluid, suggesting that reductions in CVP and hypotension might represent direct vasodilation. ET besides produced marked tachycardia, consequent with increased cAMP in cardiac pacemaker cells, simply did not change LVEF (51). Finally, despite hypotension, ET produced 10-fold increases in urine output besides as hyponatremia, suggesting renal tubular dysfunction (42). In rats administered ET, echocardiography demonstrated reduced preload, and lung pathology did not show extravasation of fluid (46). In a perfused rat center model, ET increased heart rate and coronary menstruum, the latter once over again consistent with direct vasodilation. ET too increased myocardial tissue and effluent cAMP levels (52). Monoclonal antibody directed against PA or adefovir, a nucleoside that inhibits EF adenylcyclase action, inhibited these changes. ETs could also potentially contribute to vasopressor-resistant shock because agents that stimulate intracellular campsite likewise blunt the effects of vasopressors.
Cell wall.
Although lethal LT or ET challenges do not stimulate inflammatory mediator release, alive B. anthracis challenge does, and this may contribute to shock and organ injury with anthrax (53, 54). Emerging prove suggests that peptidoglycan from anthrax jail cell wall contributes to this inflammatory response. Whole anthrax cell wall was shown originally to stimulate TNF-α, IL-1β, and IL-6 release from human peripheral blood mononuclear cells (55). A subsequent written report suggested that this activity was related to stimulation of cell surface TLR2/6 heterodimers (56). Purification of cell wall showed that its immunostimulatory outcome was primarily related to peptidoglycan (57). Peptidoglycan was also shown to exist shed past replicating bacteria. In vitro infection with anthrax besides results in NOD-2–dependent IL-1β release (58). Challenge with whole anthrax prison cell wall in rats produced dose-dependent increases in lethality, lactate and circulating inflammatory cytokines, chemokine and nitric oxide levels, and thrombocytopenia (59). Thus, anthrax prison cell wall could produce a robust intravascular inflammatory response and hemodynamic and organ dysfunction. Patients and animals dying with anthrax accept very high bacterial loads, the breakdown of which could contribute to shock (56, 57).
Proteases.
B. anthracis produces proteases other than LF that may contribute to daze and tissue injury. In civilisation studies, the delta Ames (pXO1− and pXO2−) anthrax strain produced metalloproteases belonging to the M4 thermolysin and M9 bacterial collagenase families (60). Purified preparations of these proteases produced hemorrhagic tissue injury in mice. Furthermore, chemical inhibitors or immune serum against the metalloproteases improved survival in animals challenged with Sterne strain spores. Additional studies of such proteases have implicated them in other pathophysiologic effects (61).
Secondary changes with anthrax infection that may contribute to shock.
Although anthrax produces several components potentially contributing to shock and organ injury, secondary changes may complicate this movie. For instance, lymph node involvement may disrupt lymphatic function and contribute to fluid extravasation noted clinically. Intestinal perforation with gastrointestinal anthrax and tissue breakdown or infection with nonanthrax strains in injectional anthrax may besides complicate shock and tissue injury. Differentiating primary from secondary mechanisms in such patients may be hard.
Diagnostic Methods
Based on CDC recommendations, a confirmed anthrax case is defined equally a clinically compatible one with isolation of B. anthracis or with at least ii positive supportive tests using serologic or other methods (Tabular array ane) (62). Routine culture with confirmation past immunohistochemical staining or real-time PCR is most often employed for diagnosis. There is a range of other tests that can be used to identify the bacteria or the toxin components (Table 1). B. anthracis can be isolated from numerous clinical samples, including blood, peel lesion exudates, cerebrospinal fluid, pleural fluid, sputum, and feces. Even so, prior antimicrobial therapy greatly reduces this sensitivity. Appropriate therapy can effect in negative claret cultures within half dozen to 12 hours of assistants, although the exact frequency with which this occurs is unknown. Anthrax should be considered immediately if Gram stain of specimens reveals gram-positive bacilli growing in chains (63). Suspected isolates should exist sent to a Laboratory Response Network reference laboratory for testing, and local or state health departments should be notified (64, 65). Laboratories in the Laboratory Response Network provide the supportive testing necessary to confirm an anthrax diagnosis.
TABLE ane.
SUMMARY OF DIAGNOSTIC AND SUPPORTIVE TESTS EMPLOYED TO Confirm THE DIAGNOSIS OF ANTHRAX IN CLINICALLY Compatible CASES
| Test | Description |
| Routine culture | Morphology, hemolysis, motility, and sporulation are evaluated after plating suspected Bacillus anthracis cells on standard v% sheep claret or chocolate agar. B. anthracis colonies will exist 2–5 mm in diameter with irregularly round borders and a ground drinking glass appearance, are nonhemolytic and nonmotile, and should sporulate eighteen–24 h after incubation at 35–37°C in a non-COtwo environment |
| Immunohistochemical staining (Gram stain) | Detection of B. anthracis cells in formalin-stock-still tissues using antibodies specific for cell wall or capsule antigens |
| Real-time PCR | Targets iii singled-out loci on the B. anthracis chromosome and each of the 2 virulence plasmids |
| Capsule staining | Republic of india ink, McFadyean staining, or straight fluorescence assay may be used to visualize encapsulated B. anthracis in culture or directly in clinical specimens |
| Susceptibility to gamma phage lysis | Gamma phage specifically lyses B. anthracis vegetative cells and can be used to confirm diagnosis for isolates with a concominant positive sheathing stain |
| Time-resolved fluorescence | Anti-PA assay similar to ELISA but that uses detector antibodies labeled with fluorescing lanthanide chelates instead of enzymes and pulses of excitation energy to measure fluorescence |
| Immunochromatography (Redline Warning) | A lateral period immunoassay containing a monoclonal antibody that is specific for the presence of a cell surface protein found in B. anthracis vegetative cells and used for rapid presumptive identification of B. anthracis from nonhemolytic Bacillus colonies cultured on sheep claret agar plates |
| Directly fluorescent analysis | Two-component analysis that uses fluorescein-labeled monoclonal antibodies to detect the galactose/North-acetylglucosamaine jail cell-wall–associated polysaccharide and capsule produced by B. anthracis vegetative cells in culture or directly in clinical specimens |
| Fluorescence resonance free energy transfer assay | Fluorogenic peptide-based assay used to screen for B. anthracis lethal cistron protease action |
| Europium nanoparticle-based immunoassay | Nanoparticle-based detection of antibody response against the protective antigen anthrax toxin protein |
| Electrophoretic immunotransblot reaction | Measures antibiotic protective antigen and/or lethal factor bands in serum from patients with suspected B. anthracis infection |
| Quantitative human anti-PA IgG ELISA | Enzyme-based colorimetric detection of antibody response against the protective antigen (PA) anthrax toxin protein |
| Molecular characterization | Multi-locus variable-number tandem echo analysis and sequencing of genes coding for 16S ribosomal RNA may be conducted for species identification and molecular characteristization B. anthracis isolates |
Management
Active Disease
Given the potential severity of anthrax infection, the first suspicion of disease must prompt antibiotic handling pending confirmed diagnosis (four). B. anthracis is susceptible to a variety of antimicrobial agents, including penicillin, chloramphenicol, tetracycline, erythromycin, streptomycin, fluoroquinolones, and cefazolin, along with other get-go-generation cephalosporins. Anthrax is resistant to many later-generation cephalosporins, such as cefuroxime, cefotaxime, ceftazidime, aztreonam, and trimethoprim-sulfamethoxazole (66). Table two summarizes the empiric antibiotic handling recommendations for patients with suspected anthrax infection. Although antibiotics are important in the management of B. anthracis, their efficacy might not merely be due to bacterial clearance. Information technology is possible that agents such as clindamycin used in the 2001 outbreak besides inhibit protein or RNA synthesis necessary for toxin production (67). However, while this has been shown for some types of gram-positive bacteria, it has not been demonstrated for anthrax. Aside from antimicrobial therapy, at that place are a number of potential adjunctive interventions for active anthrax: agents designed to straight inhibit toxin, thoracentesis to remove a potential reservoir of toxin, and the use of glucocorticoids. Before antimicrobials, passive immunization with antiserum was used to treat anthrax. A recent systematic review of inhalational anthrax suggested that antiserum reduced bloodshed (28). However, this finding may exist confounded by improvements in antibiotic and other supportive measures. In the Us, two antibody preparations are potentially bachelor. One is derived from individuals previously vaccinated with anthrax vaccine adsorbed (AVA) vaccine and is termed anthrax immune globulin (AIG) (Cangene, Winnipeg, MB, Canada). Treatment with AIG was associated with survival in one of two recent cases of severe inhalational anthrax every bit well as in a case of gastrointestinal anthrax (25, 68). Several patients in the injectional anthrax outbreak in the United kingdom received AIG, although the results have not been reported. AIG is available from the CDC (69). The second preparation is a man monoclonal antibody generated against recombinant PA, raxibacumab (ABthrax; Human Genome Science, Rockville, MD). This antibody improved outcome in lethal toxin–challenged or spore-challenged animal models and appears to be condom in good for you humans (70, 71).
TABLE ii.
Antibody Direction FOR ADULTS WITH ANTHRAX INFECTION
| Clinical Syndrome | Initial Therapy* † ‡ | Comment |
| Cutaneous | Ciprofloxacin 500 mg orally twice daily or doxycycline 100 mg orally twice daily for 60 d | If systemic illness or extensive edema involving face or cervix present, and so treat using regimen for inhalational anthrax |
| Inhalational, gastrointestinal, or injectional | Ciprofloxacin 400 mg intravenously every 8 h or doxycycline 100 mg intravenously every 12 h combined with second agent: clindamycin 600 mg itravenously every viii h or penicillin G 4 MU every 4–half-dozen h or meropenem1 gm intravenously every half dozen–eight h or rifampin 300 mg every 12 h | Clindamycin recommended for possible part in preventing toxin production. If meningitis is suspected, then ciprofloxacin is favored over doxycycline, and penicillin or rifampin should be administered |
Pleural fluid drainage may be of import in the management of inhalational anthrax cases to improve respiratory role and to remove a potential toxin reservoir. This intervention was potentially constructive in several recent cases of inhalational anthrax as well as in a review of cases from 1900 to 2005 (25, 28, 72). In this latter review of 70 cases, 10 of 12 surviving patients received pleural fluid drainage along with other therapy.
Based upon case reports, glucocorticoids may serve as an adjunctive therapy for patients with cutaneous anthrax and extensive edema involving the head and cervix (39, 73, 74). Glucocorticoid therapy can also be considered in patients with meningoencephalitis (94% bloodshed rate in one big case series); however, this recommendation is based solely on the clinical experience of treating meningitis of other bacterial etiologies (4, 75).
Although the management of injectional anthrax is evolving, ambitious surgery with debridement may be necessary when in that location is a clinical need to control soft tissue infection (38, 76). Drainage of extravascular fluid collections when present may also be important.
Postexposure Prophylaxis
A recent CDC briefing on anthrax postexposure prophylaxis recommended treatment with 60 days of oral ciprofloxacin or doxycycline as equivalent first-line agents (77). In addition to oral antimicrobial therapy, the CDC calls for treatment of adults with AVA (Biothrax, Emergent Biosolutions, Rockville, Medico) administered at time 0 and at ii and 4 weeks (78). AVA and anthrax vaccine precipitated (Wellness Protection Bureau, Porton Down, United kingdom of great britain and northern ireland) are aluminum hydroxide–precipitated preparations of PA from attenuated, nonencapsulated B. anthracis Sterne strain (79, eighty). AVA is licensed past the FDA for preexposure prophylaxis confronting inhalational anthrax in persons at occupational risk of disease, although it has not been studied clinically (81). In nonhuman primates challenged with aerosolized B. anthracis spores, animals that received postexposure vaccination with AVA in improver to antibiotics had a greater survival charge per unit when rechallenged with anthrax (82). Guidelines continue to recommend AVA for postexposure prophylaxis along with antibiotics for lx days because the vaccine may provide benefits and appears to have an excellent safety contour (iv). Although local reactions at the time of vaccination are described, long-term adverse events accept not been clearly documented (83).
Infection Control Considerations
Because there are no documented cases of person-to-person transmission of anthrax (including during the 2001 anthrax attack), respiratory isolation for hospitalized patients is not required. Additional details regarding appropriate infection control measures and anthrax are outlined elsewhere (Table 3) (4).
Table iii.
HEALTH Care AND INTENSIVE Care UNIT CONSIDERATIONS
| Use standard bulwark precautions. High-efficiency particulate air filter masks or other measures for airborne protection are not required. |
| Use contact isolation precautions for patients with draining anthrax lesions. |
| Immunization or postexposure prophylaxis is not required for healthcare workers or household contacts unless exposed to an droplets or surface contagion. |
| Dressings from draining anthrax lesions should be disposed of as biohazardous waste. |
| Individuals coming in direct contact with a substance potentially containing Bacillus anthracis should launder exposed skin and clothing thoroughly with soap and water. |
| A standard hospital disinfectant (e.g., hypochlorite) is adequate to clean environmental surfaces potentially contaminated with infected body fluids. |
| Human and animal remains infected with B. anthracis should exist burned. |
Conclusions
Although anthrax infection is rare in developed countries, the potential for big outbreaks persists, whether related to bioterrorism or injectional drug use. Its infrequency and nonspecific early on symptomatology suggest that, in the event of an outbreak, many patients may present with advanced disease, which has proven difficult to treat. Further defining the mechanisms underlying later-stage anthrax and developing effective management strategies that can exist administered on a wide scale are necessary.
Supplementary Fabric
Footnotes
References
1. Wenner KA, Kenner JR. Anthrax. Dermatol Clin 2004;22:247–256 [PubMed] [Google Scholar]
2. Carr KA, Lybarger SR, Anderson EC, Janes BK, Hanna PC. The role of bacillus anthracis germinant receptors in germination and virulence. Mol Microbiol 2010;75:365–375 [PubMed] [Google Scholar]
3. Hanna P. Anthrax pathogenesis and host response. Curr Top Microbiol Immunol 1998;225:13–35 [PubMed] [Google Scholar]
4. Inglesby TV, O'Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, Gerberding J, Hauer J, Hughes J, et al. Biodefense WGoC. Anthrax as a biological weapon, 2002: updated recommendations for direction. JAMA 2002;287:2236–2252 [PubMed] [Google Scholar]
5. Friedlander AM. Tackling anthrax. Nature 2001;414:160–161 [PubMed] [Google Scholar]
6. Makino S, Uchida I, Terakado North, Sasakawa C, Yoshikawa Thousand. Molecular characterization and poly peptide analysis of the cap region, which is essential for encapsulation in bacillus anthracis. J Bacteriol 1989;171:722–730 [PMC free article] [PubMed] [Google Scholar]
7. Turk Exist. Manipulation of host signalling pathways by anthrax toxins. Biochem J 2007;402:405–417 [PubMed] [Google Scholar]
8. Leppla SH. Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic amp concentrations of eukaryotic cells. Proc Natl Acad Sci USA 1982;79:3162–3166 [PMC free commodity] [PubMed] [Google Scholar]
nine. Moayeri M, Leppla SH. Cellular and systemic effects of anthrax lethal toxin and edema toxin. Mol Aspects Med 2009;30:439–455 [PMC gratis article] [PubMed] [Google Scholar]
10. Sherer Yard, Li Y, Cui X, Eichacker PQ. Lethal and edema toxins in the pathogenesis of bacillus anthracis septic daze: implications for therapy. Am J Respir Crit Care Med 2007;175:211–221 [PMC gratis article] [PubMed] [Google Scholar]
11. Shafazand S, Doyle R, Ruoss S, Weinacker A, Raffin TA. Inhalational anthrax: epidemiology, diagnosis, and management. Chest 1999;116:1369–1376 [PubMed] [Google Scholar]
12. Demirdag K, Ozden Thousand, Saral Y, Kalkan A, Kilic SS, Ozdarendeli A. Cutaneous anthrax in adults: a review of 25 cases in the eastern Anatolian region of Turkey. Infection 2003;31:327–330 [PubMed] [Google Scholar]
13. Jernigan DB, Raghunathan PL, Bell BP, Brechner R, Bresnitz EA, Butler JC, Cetron M, Cohen M, Doyle T, Fischer M, et al. Investigation of bioterrorism-related anthrax, The states, 2001: epidemiologic findings. Emerg Infect Dis 2002;eight:1019–1028 [PMC complimentary article] [PubMed] [Google Scholar]
14. Gold H. Anthrax: a written report of one hundred seventeen cases. AMA Curvation Intern Med 1955;96:387–396 [PubMed] [Google Scholar]
15. Doganay M, Metan M, Alp E. A review of cutaneous anthrax and its outcome. J Infect Public Health 2010;3:98–105 [PubMed] [Google Scholar]
16. Centers for Illness Control and Prevention (CDC) Emergency preparedness and response: specific hazards: bioterrorism: anthrax: gastrointestinal anthrax [Internet] [accessed 2011 June 13]. Available from: http://www.bt.cdc.gov/agent/anthrax/gi/
17. Kanafani ZA, Ghossain A, Sharara AI, Hatem JM, Kanj SS. Endemic gastrointestinal anthrax in 1960s Lebanon: clinical manifestations and surgical findings. Emerg Infect Dis 2003;9:520–525 [PMC free article] [PubMed] [Google Scholar]
18. Centers for Disease Control and Prevention (CDC) Gastrointestinal anthrax afterwards an beast-hide drumming result: New Hampshire and Massachusetts, 2009. MMWR Morb Mortal Wkly Rep 2010;59:872–877 [PubMed] [Google Scholar]
19. Klempner MS, Talbot EA, Lee SI, Zaki S, Ferraro MJ. Case records of the Massachusetts Full general Hospital. Instance 25–2010: a 24-year-old woman with intestinal pain and shock. N Engl J Med 2010;363:766–777 [PubMed] [Google Scholar]
20. Sirisanthana T, Chocolate-brown AE. Anthrax of the alimentary canal. Emerg Infect Dis 2002;eight:649–651 [PMC free article] [PubMed] [Google Scholar]
21. Brachman PS. Inhalation anthrax. Ann Due north Y Acad Sci 1980;353:83–93 [PubMed] [Google Scholar]
22. Plotkin SA, Brachman PS, Utell M, Bumford FH, Atchison MM. An epidemic of inhalation anthrax, the first in the twentieth century. I. Clinical features. Am J Med 1960;29:992–1001 [PubMed] [Google Scholar]
24. Suffin SC, Carnes WH, Kaufmann AF. Inhalation anthrax in a home craftsman. Hum Pathol 1978;9:594–597 [PubMed] [Google Scholar]
25. Walsh JJ, Pesik N, Quinn CP, Urdaneta V, Dykewicz CA, Boyer AE, Guarner J, Wilkins P, Norville KJ, Barr JR, et al. A case of naturally caused inhalation anthrax: clinical care and analyses of anti-protective antigen immunoglobulin g and lethal gene. Clin Infect Dis 2007;44:968–971 [PubMed] [Google Scholar]
26. Abramova FA, Grinberg LM, Yampolskaya OV, Walker DH. Pathology of inhalational anthrax in 42 cases from the sverdlovsk outbreak of 1979. Proc Natl Acad Sci USA 1993;xc:2291–2294 [PMC free commodity] [PubMed] [Google Scholar]
27. Kyriacou DN, Stein Ac, Yarnold PR, Courtney DM, Nelson RR, Noskin GA, Handler JA, Frerichs RR. Clinical predictors of bioterrorism-related inhalational anthrax. Lancet 2004;364:449–452 [PubMed] [Google Scholar]
28. Holty JE, Bravata DM, Liu H, Olshen RA, McDonald KM, Owens DK. Systematic review: a century of inhalational anthrax cases from 1900 to 2005. Ann Intern Med 2006;144:270–280 [PubMed] [Google Scholar]
29. Ross J. The pathogenesis of anthrax following the administration of spores by the respiratory road. J Pathol Bacteriol 1957;73:485–494 [Google Scholar]
30. Ringertz SH, Høiby EA, Jensenius M, Maehlen J, Caugant DA, Myklebust A, Fossum K. Injectional anthrax in a heroin skin-popper. Lancet 2000;356:1574–1575 [PubMed] [Google Scholar]
34. Radun D, Bernard H, Altmann Thou, Schöneberg I, Bochat V, van Treeck U, Rippe RM, Grunow R, Elschner G, Biederbick W, et al. Preliminary case written report of fatal anthrax in an injecting drug user in North-Rhine-Westphalia, Deutschland, December 2009. Euro Surveill 2010;xv:19464. [PubMed] [Google Scholar]
35. Del Giudice P. Cutaneous complications of intravenous drug abuse. Br J Dermatol 2004;150:1–x [PubMed] [Google Scholar]
37. Moustoukas NM, Nichols RL, Smith JW, Garey RE, Egan RR. Contaminated street heroin: relationship to clinical infections. Arch Surg 1983;118:746–749 [PubMed] [Google Scholar]
38. Booth MG, Hood J, Brooks TJ, Hart A. Network obotHPSAC. Anthrax infection in drug users. Lancet 2011;375:1345–1346 [PubMed] [Google Scholar]
39. Doganay M, Bakir M, Dokmetas I. A example of cutaneous anthrax with toxaemic stupor. Br J Dermatol 1987;117:659–662 [PubMed] [Google Scholar]
twoscore. Kuehnert MJ, Doyle TJ, Hill HA, Bridges CB, Jernigan JA, Dull PM, Reissman DB, Ashford DA, Jernigan DB. Clinical features that discriminate inhalational anthrax from other acute respiratory illnesses. Clin Infect Dis 2003;36:328–336 [PubMed] [Google Scholar]
41. Cui X, Moayeri M, Li Y, Li Ten, Haley K, Fitz Y, Correa-Araujo R, Banks SM, Leppla SH, Eichacker PQ. Lethality during continuous anthrax lethal toxin infusion is associated with circulatory stupor merely not inflammatory cytokine or nitric oxide release in rats. Am J Physiol Regul Integr Comp Physiol 2004;286:R699–R709 [PubMed] [Google Scholar]
42. Sweeney DA, Cui X, Solomon SB, Vitberg DA, Migone TS, Scher D, Danner RL, Natanson C, Subramanian GM, Eichacker PQ. Anthrax lethal and edema toxins produce unlike patterns of cardiovascular and renal dysfunction and synergistically subtract survival in canines. J Infect Dis 2010;202:1885–1896 [PMC complimentary article] [PubMed] [Google Scholar]
43. Bolcome RE, III, Chan J. Constitutive mek1 activation rescues anthrax lethal toxin-induced vascular furnishings in vivo. Infect Immun 2010;78:5043–5053 [PMC gratuitous article] [PubMed] [Google Scholar]
44. Gozes Y, Moayeri M, Wiggins JF, Leppla SH. Anthrax lethal toxin induces ketotifen-sensitive intradermal vascular leakage in certain inbred mice. Infect Immun 2006;74:1266–1272 [PMC costless article] [PubMed] [Google Scholar]
45. Rolando Thou, Stefani C, Flatau G, Auberger P, Mettouchi A, Mhlanga M, Rapp U, Galmiche A, Lemichez E. Transcriptome dysregulation by anthrax lethal toxin plays a key part in induction of human endothelial cell cytotoxicity. Cell Microbiol 2010;12:891–905 [PubMed] [Google Scholar]
46. Watson LE, Mock J, Lal H, Lu Chiliad, Bourdeau RW, Tang WJ, Leppla SH, Dostal DE, Frankel AE. Lethal and edema toxins of anthrax induce distinct hemodynamic dysfunction. Front Biosci 2007;12:4670–4675 [PubMed] [Google Scholar]
47. Kandadi MR, Hua Y, Ma H, Li Q, Kuo SR, Frankel AE, Ren J. Anthrax lethal toxin suppresses murine cardiomyocyte contractile function and intracellular Ca2+ handling via a nadph oxidase-dependent mechanism. PLoS One 2010;5:e13335. [PMC costless article] [PubMed] [Google Scholar]
48. Li Y, Cui X, Su J, Haley M, Macarthur H, Sherer K, Moayeri Thou, Leppla SH, Fitz Y, Eichacker PQ. Norepinephrine increases blood pressure just not survival with anthrax lethal toxin in rats. Crit Care Med 2009;37:1348–1354 [PMC free article] [PubMed] [Google Scholar]
49. Griffith TM, Taylor HJ. Circadian amp mediates edhf-blazon relaxations of rabbit jugular vein. Biochem Biophys Res Commun 1999;263:52–57 [PubMed] [Google Scholar]
50. Stehlik J, Movsesian MA. Inhibitors of cyclic nucleotide phosphodiesterase 3 and five as therapeutic agents in heart failure. Expert Opin Investig Drugs 2006;15:733–742 [PubMed] [Google Scholar]
51. Borer JS. Drug insight: if inhibitors as specific middle-charge per unit-reducing agents. Nat Clin Pract Cardiovasc Med 2004;1:103–109 [PubMed] [Google Scholar]
52. Hicks CW, Li Y, Okugawa S, Solomon SB, Moayeri Thou, Leppla SH, Mohanty A, Subramanian GM, Mignone TS, Fitz Y, Cui X, Eichacker PQ. Anthrax edema toxin has camp-mediated stimulatory furnishings and high dose lethal toxin has depressant effects in an isolated perfused rat heart model. Am J Physiol Heart Circ Physiol 2011;300:H1108–H1118 [PMC gratis article] [PubMed] [Google Scholar]
53. Chakrabarty K, Wu W, Berth JL, Duggan ES, Nagle NN, Coggeshall KM, Metcalf JP. Man lung innate immune response to bacillus anthracis spore infection. Infect Immun 2007;75:3729–3738 [PMC free article] [PubMed] [Google Scholar]
54. Stearns-Kurosawa DJ, Lupu F, Taylor FB, Jr, Kinasewitz G, Kurosawa S. Sepsis and pathophysiology of anthrax in a nonhuman primate model. Am J Pathol 2006;169:433–444 [PMC free article] [PubMed] [Google Scholar]
55. Popov SG, Villasmil R, Bernardi J, Grene E, Cardwell J, Popova T, Wu A, Alibek D, Bailey C, Alibek K. Effect of bacillus anthracis lethal toxin on homo peripheral blood mononuclear cells. FEBS Lett 2002;527:211–215 [PubMed] [Google Scholar]
56. Triantafilou M, Uddin A, Maher Due south, Charalambous N, Hamm TS, Alsumaiti A, Triantafilou Yard. Anthrax toxin evades toll-like receptor recognition, whereas its cell wall components trigger activation via tlr2/6 heterodimers. Cell Microbiol 2007;9:2880–2892 [PubMed] [Google Scholar]
57. Langer M, Malykhin A, Maeda K, Chakrabarty K, Williamson KS, Feasley CL, Due west CM, Metcalf JP, Coggeshall KM. Bacillus anthracis peptidoglycan stimulates an inflammatory response in monocytes through the p38 mitogen-activated poly peptide kinase pathway. PLoS I 2008;3:e3706. [PMC complimentary commodity] [PubMed] [Google Scholar]
58. Hsu LC, Ali SR, McGillivray Southward, Tseng PH, Mariathasan South, Humke EW, Eckmann L, Powell JJ, Nizet V, Dixit VM, et al. A nod2-nalp1 complex mediates caspase-1-dependent il-1beta secretion in response to bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U.s. 2008;105:7803–7808 [PMC free article] [PubMed] [Google Scholar]
59. Cui 10, Su J, Li Y, Shiloach J, Solomon S, Kaufman JB, Mani H, Fitz Y, Weng J, Altaweel L, et al. Bacillus anthracis jail cell wall produces injurious inflammation merely paradoxically decreases the lethality of anthrax lethal toxin in a rat model. Intensive Care Med 2010;36:148–156 [PMC free article] [PubMed] [Google Scholar]
sixty. Popov SG, Popova TG, Hopkins S, Weinstein RS, MacAfee R, Fryxell KJ, Chandhoke 5, Bailey C, Alibek Chiliad. Effective antiprotease-antibiotic treatment of experimental anthrax. BMC Infect Dis 2005;v:25. [PMC free article] [PubMed] [Google Scholar]
61. Chung MC, Jorgensen SC, Popova TG, Tonry JH, Bailey CL, Popov SG. Activation of plasminogen activator inhibitor implicates protease inha in the acute-phase response to bacillus anthracis infection. J Med Microbiol 2009;58:737–744 [PubMed] [Google Scholar]
62. Centers for Disease Control and Prevention (CDC) Update: investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001. MMWR Morb Mortal Wkly Rep 2001;50:889–893 [PubMed] [Google Scholar]
63. Centers for Affliction Control and Prevention (CDC) Update: investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, Oct 2001. MMWR Morb Mortal Wkly Rep 2001;fifty:909–919 [PubMed] [Google Scholar]
64. Morse S, Kellogg R, Perry Southward. Detecting biothreat agents: the laboratory response network. ASM News 2003;69:433 [Google Scholar]
66. Swartz MN. Recognition and direction of anthrax: an update. Northward Engl J Med 2001;345:1621–1626 [PubMed] [Google Scholar]
67. Stevens DL, Maier KA, Mitten JE. Outcome of antibiotics on toxin product and viability of clostridium perfringens. Antimicrob Agents Chemother 1987;31:213–218 [PMC gratuitous commodity] [PubMed] [Google Scholar]
68. Anaraki S, Addiman S, Nixon G, Krahe D, Ghosh R, Brooks T, Lloyd 1000, Spencer R, Walsh A, McCloskey B, et al. Investigations and control measures following a case of inhalation anthrax in e london in a pulsate maker and drummer, October 2008. Euro Surveill 2008;thirteen:19076. [PubMed] [Google Scholar]
69. Centers for Illness Control and Prevention (CDC) CDC emergency preparedness and response site [accessed 2011 July 7]. Available from: www.bt.cdc.gov/
70. Hewetson JF, Little SF, Ivins Be, Johnson WM, Pittman PR, Brown JE, Norris SL, Nielsen CJ. An in vivo passive protection assay for the evaluation of immunity in ava-vaccinated individuals. Vaccine 2008;26:4262–4266 [PubMed] [Google Scholar]
71. Migone TS, Subramanian GM, Zhong J, Healey LM, Corey A, Devalaraja Chiliad, Lo L, Ullrich Southward, Zimmerman J, Chen A, et al. Raxibacumab for the treatment of inhalational anthrax. N Engl J Med 2009;361:135–144 [PubMed] [Google Scholar]
72. Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith Yard, Tapper M, Fisk TL, Zaki Due south, Popovic T, et al. Bioterrorism-related inhalational anthrax: the first 10 cases reported in the united states. Emerg Infect Dis 2001;7:933–944 [PMC costless article] [PubMed] [Google Scholar]
73. Doust JY, Sarkarzadeh A, Kavoossi K. Corticosteroid in treatment of malignant edema of chest wall and neck (anthrax). Dis Chest 1968;53:773–774 [PubMed] [Google Scholar]
74. Sejvar JJ, Tenover FC, Stephens DS. Management of anthrax meningitis. Lancet Infect Dis 2005;5:287–295 [PubMed] [Google Scholar]
75. Lanska DJ. Anthrax meningoencephalitis. Neurology 2002;59:327–334 [PubMed] [Google Scholar]
76. Parcell BJ, Wilmshurst AD, France AJ, Motta L, Brooks T, Olver WJ. Injection anthrax causing compartment syndrome and necrotising fasciitis. J Clin Pathol 2011;64:95–96 [PubMed] [Google Scholar]
77. Stern EJ, Uhde KB, Shadomy SV, Messonnier Due north. Briefing written report on public health and clinical guidelines for anthrax. Emerg Infect Dis 2008;14:07–0969 [PMC free article] [PubMed] [Google Scholar]
78. Centers for Disease Control and Prevention (CDC) Use of anthrax vaccine in response to terrorism: supplemental recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep 2002;51:1024–1026 [PubMed] [Google Scholar]
eighty. Baillie Fifty. The development of new vaccines against bacillus anthracis. J Appl Microbiol 2001;91:609–613 [PubMed] [Google Scholar]
81. Bartlett JG, Inglesby TV, Jr, Borio L. Management of anthrax. Clin Infect Dis 2002;35:851–858 [PubMed] [Google Scholar]
82. Friedlander AM, Welkos SL, Pitt ML, Ezzell JW, Worsham PL, Rose KJ, Ivins Be, Lowe JR, Howe GB, Mikesell P, et al. Postexposure prophylaxis against experimental inhalation anthrax. J Infect Dis 1993;167:1239–1243 [PubMed] [Google Scholar]
83. Wright JG, Quinn CP, Shadomy Due south, Messonnier N. Use of anthrax vaccine in the Us: recommendations of the advisory commission on immunization practices (ACIP), 2009. MMWR Recomm Rep 2010;59:one–30 [PubMed] [Google Scholar]
84. Wood BJ, DeFranco B, Ripple M, Topiel Chiliad, Chiriboga C, Mani V, Barry One thousand, Fowler D, Masur H, Borio L. Inhalational anthrax: radiologic and pathologic findings in two cases. AJR Am J Roentgenol 2003;181:1071–1078 [PMC costless article] [PubMed] [Google Scholar]
85. Jallali N, Hettiaratchy S, Gordon AC, Jain A. The surgical direction of injectional anthrax. J Plast Reconstr Aesthet Surg 2011;64:276–277 [PubMed] [Google Scholar]
Articles from American Journal of Respiratory and Disquisitional Care Medicine are provided here courtesy of American Thoracic Society
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361358/
0 Response to "Second and Subsequent Infection of Anthrax Again After Recovery"
Post a Comment