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Anthrax.

Anthrax is an often fatal bacterial infection that occurs when Bacillus anthracis endospores enter the body through one of three major routes: inhalational, cutaneous, or gastrointestinal. Before the anthrax terrorist attacks in the United States in 2001, there was very little interest in anthrax as a serious human pathogen; anthrax was viewed mainly as a veterinarian problem of minor importance, with most cases attributed to occupational exposure. However, this cavalier attitude toward anthrax changed following the 2001 terrorist attacks. Although the number of cases was relatively small, the attacks have heightened concern about the feasibility of large-scale aerosol bioweapons attacks by terrorist groups. Many, if not most patients, would require some degree of critical care in the form of ventilator or hemodynamic support. It is for this reason that anesthesiologists and other critical care physicians have specific knowledge of the diagnosis, treatment, and prevention of anthrax.

Anthrax↗

Three rare cases of anthrax arising from the same source.

Anthrax is an acute bacterial infection caused by Bacillus anthracis. Humans become infected under natural conditions by contact with infected animals or contaminated animal products. About 95% of human anthrax is cutaneous and 5% respiratory. Gastrointestinal anthrax is very rare, and has been reported in less than 1% of all cases. Anthrax meningitis is a rare complication of any of the other three forms of disease. We report three rare cases of anthrax (gastrointestinal, oropharyngeal and meningitis) arising from the same source. The three patients were from a single family and were admitted with different clinical pictures after the ingestion of half-cooked meat from a sick sheep. These cases emphasize the need for awareness of anthrax in the differential diagnosis in areas where the disease remains endemic.

Adolescent↗

Anthrax vaccination and self-reported symptoms, functional status, and medical conditions in the National Health Survey of Gulf War Era Veterans and Their Families.

PURPOSE: To evaluate the health status of Gulf War veterans who reported receipt of anthrax vaccination and a small group of Gulf War veterans for whom documentation of anthrax vaccination exists. METHODS: Among the 11,441 Gulf War veterans who completed a health survey, 4601 reported receiving the anthrax vaccine during the war; 2979 veterans reported not receiving it; 3861 were uncertain. Also, 352 of these respondents were documented by the Department of Defense as having received anthrax vaccination. We compared the medical history of these groups of veterans using multivariate analyses. Finally, we analyzed perception of exposure and its relation to reporting bias. RESULTS: There were statistically significant differences in prevalence for almost all outcomes studied between those who reported having received anthrax vaccination and those who did not so report. However, when we compared the veterans for whom vaccination records exist to the group who self-reported that they had not received the vaccine, the significant differences in prevalence for almost all of the outcomes disappeared. CONCLUSIONS: The extent of a reporting bias should be carefully considered when one evaluates the health consequences of anthrax vaccination based on self-reported data.

Adult↗

New-onset rheumatoid arthritis after anthrax vaccination.

BACKGROUND: Anthrax vaccine was licensed in 1970 and is used to protect individuals exposed to biological warfare and those who may come in contact with Bacillus anthracis in infected animals or in laboratory settings. The current adsorbed anthrax vaccine is regarded as effective and safe. Adverse effects reported include fever, chills, myalgia, arthralgia, and nausea. Four cases of rheumatoid arthritis (RA) temporally related to anthrax vaccine have been reported. As the number of administered doses increases, a better understanding of its adverse events profile will be forthcoming. OBJECTIVE: To describe another patient with RA temporally related to anthrax vaccination. METHODS: A 42-year-old man developed bilateral knee stiffness and pain in all the proximal interphalangeal joints 5 days after receiving the first dose of anthrax vaccine. He reported chills, fever, and joint and neck pain, with a tender nodule at the injection site after dose 2. Hours after receiving dose 3 he experienced fever, chills, nausea, vomiting, and neck, hand, and shoulder pain. The vaccination series was terminated after the third dose. RESULTS: Physical examination revealed moderate swelling and tenderness of his bilateral proximal interphalangeal joints. His complete blood cell count was normal; rheumatoid factor level, 198 IU/mL; erythrocyte sedimentation rate, 53 mm/h; antinuclear antibodies, negative; C-reactive protein level, 2.7 mg/L; and anti-cyclic citrullinated peptide antibody level, 168 EU. Radiographs revealed mild degenerative changes in his hands and knees bilaterally. CONCLUSIONS: This case represents a fifth patient with RA temporally related to anthrax vaccine.

Adult↗

Immune system paralysis by anthrax lethal toxin: the roles of innate and adaptive immunity.

Since the deliberate use of anthrax as a bioweapon in the USA in 2001, an enormous amount of attention has been focused on the biology of Bacillus anthracis, the causative bacterium of anthrax. Fatal systemic anthrax involves massive bacteraemia and toxaemia with non-descript early symptoms until the onset of shock and sudden death. The outbreak of fatal symptoms after the incubation period of B anthracis suggests an impairment of the host immune system against this pathogen. Thus, it is likely that B anthracis will possess certain strategies to escape from the host immune system. However, the mechanisms of such immune-evasion strategies are not fully characterised yet. Given the critical role of B anthracis toxins in anthrax pathogenesis, much effort has been made to understand the pathological nature of the toxins. Recent studies have shown the pleiotropic actions of anthrax lethal toxin on host innate immune cells, and that several effects of anthrax lethal toxin may directly account for the mechanism of immune intervention by B anthracis.

Animals↗

Peptide inhibitors MAP the way towards fighting anthrax pathogenesis.

The pathogenesis of anthrax is such that unless antibiotic treatment is initiated at an early stage in the disease, it is ineffective against the bacteria-induced toxaemia that subverts the immune response, inflicts massive tissue damage and is ultimately the major factor contributing to death during anthrax infection. As current events have demonstrated the feasibility of the use of anthrax as a bioterrorism agent, and exemplified the difficulty of treating the ensuing infection, inhibition of anthrax toxin has become a major focus of research for the design of antitoxin therapeutics. In this issue of Biochemical Journal, Bracci and co-workers describe the discovery by competitive screening of a phage-display library of a peptide inhibitor of anthrax toxin assembly that shows great promise towards the treatment of anthrax.

Anthrax↗

A review of anthrax in Canada and implications for research on the disease in northern bison.

During the first half of the century, the majority of anthrax outbreaks in Canada occurred in the southern portions of Ontario and Quebec and were often associated with pastures contaminated by effluent from textile industries dealing with imported animal materials. In 1952, introduction of Federal regulations requiring disinfection of these materials greatly reduced the incidence of anthrax in eastern Canada. Since 1962, domestic outbreaks of the disease have been reported almost exclusively in cattle in the western prairie provinces. Between 1962 & 1993, nine anthrax epizootics have been recorded in the bison herds of the Northwest Territories and northern Alberta resulting in the deaths of at least 1309 animals. During the northern epizootics there has been a strong sex bias in mortalities with the majority of carcasses being sexually mature bulls. The northern epizootics occur during drought conditions in the late summer, preceded by a wet spring, and end with the arrival of coolers weather. It has been hypothesized that stress factors associated with these meteorological conditions coupled with breeding stress during the late summer rut may predispose the bulls to infection. Alternatively, the meteorological conditions may work to concentrate anthrax spores in the environment into low lying wallows preferentially utilized by the bulls. Recent genetic analyses of Bacillus anthracis isolates from Canada and the United States have identified that, while closely related to isolates from domestic outbreaks, isolates from northern bison epizootics form their own distinct strain. This suggests that the establishment of anthrax in northern Canada was a singular event that occurred prior to the first recognized epizootic in 1962. A review of the agricultural history of northern Canada has identified several situations in the first half of the century which may have provided the opportunity for the transfer of anthrax from cattle to the indigenous bison.

Animals↗

Cutaneous anthrax associated with facial palsy: case report and literature review.

BACKGROUND: Anthrax is primarily an animal disease. Bacillus anthracis, the causal agent in anthrax, is a Gram-positive rod. Humans can acquire anthrax by industrial exposure to infected animals or animal products. METHODS: Reported here is the case of a 48-year-old male farm worker from Iran with a history of direct contact with herds. He presented after 6 days of fever with toxicity and a crusted ulcer on the face that was later confirmed bacteriologically to be cutaneous anthrax. He was treated with large doses of intravenous penicillin and corticosteroids along with multiple subcutaneous epinephrine injections that were used to control the infection and massive facial edema. RESULTS: After 14 days, he partially recovered; however, ipsilateral facial nerve palsy developed and persisted despite therapeutic efforts. CONCLUSION: It is not possible to conclude whether early diagnosis and treatment of anthrax results in a lower risk of complications. Facial palsy can be added to the list of variable complications of the cutaneous effects of anthrax.

Adrenal Cortex Hormones↗

2001 anthrax crisis in Washington, D.C.: clinic for persons exposed to contaminated mail.

An anthrax prophylaxis clinic is described. In October 2001, four workers from the U.S. Postal Service's Brentwood facility in Washington, D.C., were hospitalized with inhalational anthrax; many others may have been exposed to anthrax spores. U.S. Public Health Service (USPHS) teams were deployed to establish an anthrax prophylaxis clinic that would provide education and medication to workers and people who visited the mail facility. The temporary clinic was set up at D.C. General Hospital and was staffed primarily by health care professionals from USPHS. The protocol at the clinic involved three major phases. Phase 1 consisted of gathering information from the patient and distributing educational materials. Phase 2 involved presentations by a physician and a pharmacist concerning anthrax, followed by a question-and-answer session. In phase 3, a pharmacist selected the most appropriate prophylactic agent, dispensed the medication, counseled the patient, and referred patients with flu-like symptoms or skin lesions to a physician. Two floor plans were used to maximize the number of patients seen per hour without jeopardizing patient care. The clinic operated 14 hours a day for 14 days. The 136-member health care team included 52 pharmacists, and medication was dispensed to more than 18,000 patients. The clinic may serve as a model for pharmacists and other professionals in designing and implementing disaster plans. A multidisciplinary team established and operated a clinic to treat persons who may have been exposed to anthrax through contaminated mail.

Ambulatory Care Facilities↗

Patient and family physician preferences for care and communication in the eventuality of anthrax terrorism.

BACKGROUND: The threat of bioterrorism consequent to the September 11, 2001 attack in the USA generated suggestions for improved medical response mainly through hospital preparedness. OBJECTIVES: The aim of the present study was to investigate the impact of this period of tension on patients' first choice for care and for receiving relevant information, and on primary care doctors' feelings of responsibility in the eventuality of an anthrax attack. METHODS: During October 11-31, 2001, 500 patients from 30 clinics throughout Israel were asked to complete a questionnaire on their awareness of the anthrax threat, measures taken to prepare for it, and preferred sources of care and information. Their 30 physicians, and an additional 20, completed a questionnaire on knowledge about anthrax and anthrax-related patient behaviours and clinic visits. RESULTS: The outstanding finding was the low rate (30%) of patients who chose the hospital emergency department as their first choice for care or information if they were worried about an anthrax attack or the media communicated that an attack was in progress. The other two-thirds preferred their family doctor or the health authorities. Most of the physicians (89%) felt it was their responsibility to treat anthrax-infected patients and that they should therefore be supplied with appropriate guidelines. CONCLUSION: This study suggests that in Israel, a country with a high degree of awareness of civil defence aspects, both patients and primary care doctors believe that family physicians should have a major role in the case of bioterrorist attacks. This must be seriously considered during formulation of relevant health services programmes.

Anthrax↗

A high-affinity monoclonal antibody to anthrax protective antigen passively protects rabbits before and after aerosolized Bacillus anthracis spore challenge.

We have developed a therapeutic for the treatment of anthrax using an affinity-enhanced monoclonal antibody (ETI-204) to protective antigen (PA), which is the central cell-binding component of the anthrax exotoxins. ETI-204 administered preexposure by a single intravenous injection of a dose of between 2.5 and 10 mg per animal significantly protected rabbits from a lethal aerosolized anthrax spore challenge ( approximately 60 to 450 times the 50% lethal dose of Bacillus anthracis Ames). Against a similar challenge, ETI-204 administered intramuscularly at a 20-mg dose per animal completely protected rabbits from death (100% survival). In the postexposure setting, intravenous administration of ETI-204 provided protection 24 h (8 of 10) and 36 h (5 of 10) after spore challenge. Administration at 48 h postchallenge, when 3 of 10 animals had already succumbed to anthrax infection, resulted in the survival of 3 of 7 animals (43%) for the duration of the study (28 days). Importantly, surviving ETI-204-treated animals were free of bacteremia by day 10 and remained so until the end of the studies. Only 11 of 51 ETI-204-treated rabbits had positive lung cultures at the end of the studies. Also, rabbits that were protected from inhalational anthrax by administration of ETI-204 developed significant titers of PA-specific antibodies. Presently, the sole therapeutic regimen available to treat infection by inhalation of B. anthracis spores is a 60-day course of antibiotics that is effective only if administered prior to or shortly after exposure. Based upon results reported here, ETI-204 is an effective therapy for prevention and treatment of inhalational anthrax.

Animals↗

Adverse reactions to anthrax immunisation in a military field hospital.

OBJECTIVE: To determine the outcome of anthrax immunisation. METHODS: Adverse reactions (occurrence, nature, severity and incapacity) and immune responses to a voluntary programme of anthrax immunisation at 0, 3, 6, and 24 weeks were monitored by questionnaire and voluntary blood sampling in 129 members, including 24 immunised 7 years previously (immunes), of a military field hospital alerted for possible deployment. RESULTS: Follow-up was complete in 85%. Ninety-eight (76%) received the first anthrax immunisation. Uptake was greater (p = 0.015) in immunes. Initial prevalence of adverse reaction was 63%. Subsequent uptake and adverse reaction dwindled significantly (p < 0.001). Only 28 (22%) were immunised at 24 weeks. Proportions reporting adverse reactions following the initial immunisation were greater in immunes (p = 0.046) and officers (p = 0.02). There was no significant (p = 0.36) correlation between uptake of immunisation and prevalence of adverse reaction. Antecedent adverse reaction did not reduce the proportion of participants accepting immunisation subsequently. The nature of adverse reactions (47% local, 24% systemic and 27% both) and severity were the same throughout. Forty-five percent of adverse reactions caused incapacity. Seventy-four percent of these had pain in the injected arm (+/- systemic symptoms) which prevented lifting or driving for 48 hours in 63%. Immune responses were greater in immunes. CONCLUSIONS: It was concluded that anthrax immunisation results in a higher than expected prevalence of adverse reaction with initial incapacity of military significance affecting 18%. Greater immune responses may increase adverse reaction but this does not affect acceptance of anthrax immunisation. Poor completion rates necessitate development of a new anthrax immunisation strategy.

Adult↗

Anthrax meningoencephalitis.

OBJECTIVE: To review reported cases of anthrax meningoencephalitis and describe the clinical findings, diagnostic test results, treatment, and outcome over the past 50 years. METHODS: Retrospective review of English language articles published since Haight's (1952) review. RESULTS: Thirty-four core articles were identified, describing 70 patients with cutaneous (29%), gastrointestinal (17%), inhalational (39%), and unknown (16%) sources of infection. Clinical signs on presentation included fever, malaise, meningeal signs, hyperreflexia, and delirium, stupor, or coma. CSF analyses demonstrated hemorrhagic meningitis, with positive Gram's stains and CSF cultures. Many patients presented in extremis following a prodromal period of 1 to 6 days, and 75% died within 24 hours of presentation. Despite aggressive treatment in many cases, only 6% (4 of 70) survived, none of whom had pulmonary anthrax. Surviving patients generally had a cutaneous portal of entry, were younger, and had less severely abnormal initial CSF results than patients who died. Most of the survivors recovered fully. Pathologic findings included hemorrhagic meningitis, multifocal subarachnoid and intraparenchymal hemorrhages, vasculitis, and cerebral edema. CONCLUSIONS: Anthrax meningoencephalitis has a high case-fatality rate, even with aggressive antibiotic treatment and supportive therapy. Hemorrhagic meningitis should raise suspicion of anthrax infection, particularly if gram-positive rods are demonstrated on Gram's stain. Anthrax meningoencephalitis can develop from any primary focus, but survival appears to be most likely if meningoencephalitis develops from cutaneous anthrax. Treatment of surviving patients was generally begun before signs and symptoms of meningoencephalitis were present.

Anthrax↗

The primary care differential diagnosis of inhalational anthrax.

PURPOSE: Inhalational anthrax is an extremely rare infectious disease with nonspecific initial symptoms, thus making diagnosis on clinical grounds difficult. After a covert release of anthrax spores, primary care physicians will be among the first to evaluate cases. This study defines the primary care differential diagnosis of inhalational anthrax. METHODS: In May 2002, we mailed survey instruments consisting of 3 randomly chosen case vignettes describing patients with inhalational anthrax to a nationwide random sample of 665 family physicians. Nonrespondents received additional mailings. Physicians were asked to provide their most likely nonanthrax diagnosis for each case. RESULTS: The response rate was 36.9%. Diagnoses for inhalational anthrax were grouped into 35 diagnostic categories, with pneumonia (42%), influenza (10%), viral syndrome (9%), septicemia (8%), bronchitis (7%), central nervous system infection (6%), and gastroenteritis (4%) accounting for 86% of all diagnoses. Diagnoses differed significantly between cases that proved to be fatal and those that proved to be nonfatal. CONCLUSIONS: Inhalational anthrax resembles common diagnoses in primary care. Surveillance systems for early detection of bioterrorism events that rely only on diagnostic codes will be hampered by false-positive alerts. Consequently, educating frontline physicians to recognize and respond to bioterrorism is of the highest priority.

Anthrax↗

Media exposure to bioterrorism: stress and the anthrax attacks.

This study examined media exposure and adjustment to anthrax bioterrorism attacks and the terrorist attacks on 9/11 in a sample of 300 people who lived distant from the attacks. Measures of direct and indirect exposure to terrorism, perceived risk of anthrax exposure, psychological distress, and outlook were assessed at 2 to 3 months and at 8 months after the first reported anthrax attack. Initial anthrax media exposure was a powerful predictor of distress, whereas subsequent anthrax media exposure only predicted negative changes in outlook over time. Perceived risk of anthrax exposure predicted distress and outlook but did not appear to mediate the effects of media exposure. Determining the nature and consequences of media exposure to threatening and frightening events like terrorism will help predict and manage response to future bioterrorism.

Adaptation, Psychological↗

Serological studies of patients with cutaneous and oral-oropharyngeal anthrax from northern Thailand.

An outbreak of 52 cases of cutaneous anthrax and 24 cases of oral-oropharyngeal anthrax occurred in rural Northern Thailand in 1982, caused by contaminated water buffalo meat. Microbiologic diagnosis of many of these cases was hindered by delayed presentation for care and by prior antibiotic therapy. In a retrospective investigation, we used enzyme-linked immunosorbent assays to measure antibody titers to components of anthrax edema toxin (edema factor [EF] and protective antigen [PA]), lethal toxin (lethal factor [LF] and PA), and poly-D-glutamic acid capsule. Electrophoretic-immunotransblots (EITB, Western blot) were used to detect antibodies to PA and LF. Nine patients with cutaneous anthrax, 10 patients with oral-oropharyngeal anthrax, and 43 healthy unexposed Thai control villagers were studied. Over all, EITB was positive in 13/18 patients (sensitivity 72%) and 0/43 controls (specificity 100%). The sensitivity of the ELISA was 72% for PA, 42% for LF, 26% for EF, and 95-100% for capsule. Although a few control sera had apparent false positive titers to PA, the specificity of the ELISA confirmed by EITB (100%) demonstrated the applicability of these tests for the diagnosis of anthrax.

Adolescent↗

Surveillance for adverse events associated with anthrax vaccination--U.S. Department of Defense, 1998-2000.

Concerns about the potential use of anthrax as a biologic weapon prompted the U.S. Department of Defense (DoD) to announce on December 15, 1997, anthrax vaccination of all U.S. military personnel. This effort is coordinated by the Anthrax Vaccine Immunization Program (AVIP). AVIP plans a phased vaccination process to achieve total force protection against anthrax by 2004. The current phase of implementation includes vaccination of all service members and mission-essential DoD civilian employees assigned or deployed to high-threat areas. On the basis of program monitoring, as of April 12, 2000, 425,976 service members had received 1,620,793 doses of anthrax vaccine adsorbed (AVA) (Bioport, Inc., Lansing, Michigan). Some service members have cited concerns about vaccine safety and efficacy in their decision to refuse vaccination, despite the possibility of administrative or disciplinary actions. To assess anthrax vaccination safety, DoD has conducted surveys of vaccinated personnel. This report describes three completed or ongoing surveys. The findings indicate that rates of local reactions were higher in women than men and that no patterns of unexpected local or systemic adverse events have been identified.

Adverse Drug Reaction Reporting Systems↗

Human anthrax in India: urgent need for effective prevention.

Anthrax is a zoonotic illness caused by Bacillus anthracis. Sporadic cases continue to be reported from many parts of the world. From India, both sporadic cases and outbreaks are being reported regularly. The Union Territory of Pondicherry (a former French colony) lies on the coast of Bay of Bengal, where the incidence of anthrax is on the rise with 28 cases being detected in the year 1999 and 2000 alone. So far, about 34 human cases have been encountered in this region. Recently, an increase in the number of anthrax cases has been noted in veterinary and human practice in this area. Most cases have occurred in agricultural labourers who gave history of handling animal meat or skin of infected animals. The meningitic form of the disease has a very bad prognosis. Patients with this form of disease died despite treatment with high dose penicillin. The typical bacilli were seen in the CSF in all cases of anthrax meningitis and was diagnostic of the condition. The cutaneous form of illness had a benign course and responded favourably to penicillin treatment. Awareness among clinicians and mandatory reporting of cases to public health departments along with public education will help control morbidity and mortality due to anthrax. Effective immunization of animals is the other important control measure for anthrax.

Animals↗