Bacillus anthracis

Dev Biol (Basel), 2002, 111, 321 - 6
Novel in vitro functional assays for the determination of anthrax toxin components; Hallis B et al.; The characterisation and evaluation of the UK licensed human anthrax vaccine depends on several in vivo tests that determine its safety and potency . Assays for the determination of functionally active and/or immunoreactive toxin components and S-layer proteins have been developed and applied to the characterisation of anthrax vaccine . These technologies may support production of consistent and effective vaccines, and may ultimately reduce the requirements for in vivo testing.

J Biol Chem, 2003 Jul 11, 278(28), 25990 - 7 Epub 2003 Apr 03.
Structure-based inhibitor discovery against adenylyl cyclase toxins from pathogenic bacteria that cause anthrax and whooping cough; Soelaiman S et al.; Edema factor (EF) and CyaA are adenylyl cyclase toxins secreted by pathogenic bacteria that cause anthrax and whooping cough, respectively . Using the structure of the catalytic site of EF, we screened a data base of commercially available, small molecular weight chemicals for those that could specifically inhibit adenylyl cyclase activity of EF . From 24 compounds tested, we have identified one quinazoline compound, ethyl 5-aminopyrazolo{1,5-a}quinazoline-3-carboxylate, that specifically inhibits adenylyl cyclase activity of EF and CyaA with approximately 20 microm Ki . This compound neither affects the activity of host resident adenylyl cyclases type I, II, and V nor exhibits promiscuous inhibition . The compound is a competitive inhibitor, consistent with the prediction that it binds to the adenine portion of the ATP binding site on EF . EF is activated by the host calcium sensor, calmodulin . Surface plasmon resonance spectroscopic analysis shows that this compound does not affect the binding of calmodulin to EF . This compound is dissimilar from a previously described, non-nucleoside inhibitor of host adenylyl cyclase . It may serve as a lead to design antitoxins to address the role of adenylyl cyclase toxins in bacterial pathogenesis and to fight against anthrax and whooping cough.

J Occup Environ Med, 2003 Mar, 45(3), 222 - 33
Analysis of adverse events after anthrax immunization in US Army medical personnel; Wasserman GM et al.; A broad range of health effects in a cohort of 601 health care personnel, immunized with anthrax vaccine adsorbed (AVA) as a military occupational health requirement, were assessed to evaluate adverse events both qualitatively and quantitatively . Active surveillance showed that localized reactions were common and occurred more often in women than men . Five patients were reported to the Vaccine Adverse Event Reporting System, but only one event could be definitively attributed to immunization, a large localized reaction . Two separate cohort studies, one using nested data from a standardized health risk appraisal instrument and the other comparing rates of outpatient visits and hospitalizations, did not reveal significant differences between AVA-immunized and unimmunized individuals . Our findings suggest that AVA is relatively reactogenic but do not indicate serious adverse health effects due to immunization.

Rev Neurol (Paris), 2003 Feb, 159(2), 162 - 4
{Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome}; Gherardi RK; Macrophagic myofasciitis is a condition first reported in 1998, which cause remained obscure until 2001 . Over 200 definite cases have been identified in France, and isolated cases have been recorded in other countries . The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called chronic fatigue syndrome in about half of patients . One third of patients develop an autoimmune disease, such as multiple sclerosis . Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1*01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis . Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy . Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant used in vaccines against hepatitis B virus, hepatitis A virus, and tetanus toxoid . Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile . It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of chronic fatigue syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic chronic fatigue syndrome . Therefore, the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminium-containing vaccines) and systemic symptoms . Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf war syndrome . Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome . Indeed, both type and structure of symptoms are strikingly similar in Gulf war veterans and patients with macrophagic myofasciitis . Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War syndrome . Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminium hydroxide and, possibly, squalene, another Th-2 adjuvant . If safety concerns about long-term effects of aluminium hydroxide are confirmed it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worldwide.

Ann Emerg Med, 2003 Apr, 41(4), 447 - 52
Syndromic analysis of computerized emergency department patients' chief complaints: an opportunity for bioterrorism and influenza surveillance; Irvin CB et al.; STUDY OBJECTIVE: Emergency department computerized triage logs might be useful for automated ED surveillance and potentially for early identification of bioterrorism events . We describe a Web-based surveillance program and its feasibility for surveillance . METHODS: A Web-based surveillance program that receives computerized chief complaint data daily from a large academic urban teaching hospital and performs syndromic analysis on these data was developed . On the basis of preset limits, the Web-based surveillance program sends an alert e-mail message when the syndromic analysis reveals an increase in the number of patients in predefined symptom groups . The feasibility of this system was tested by using historical data during an influenza outbreak (December 1999 to January 2000) and applying the anthrax symptom group . RESULTS: The Web-based surveillance program identified the influenza outbreak in the first week . CONCLUSION: Computerized triage logs might be a feasible method for bioterrorism and influenza surveillance . The Web-based nature of the surveillance program creates the opportunity for other hospitals to contribute data, potentially resulting in an automated network of ED computerized triage log surveillance.

Ann Emerg Med, 2003 Apr, 41(4), 441 - 6
Medical counterbioterrorism: the response to provide anthrax prophylaxis to New York City US Postal Service employees; Partridge R et al.; STUDY OBJECTIVE: We describe and analyze a recent rapid deployment of disaster medical assistance teams and other government agencies to provide medical screening and anthrax prophylaxis to New York City US Postal Service employees potentially exposed to letters contaminated with anthrax spores . METHODS: A description of the response effort is presented . Data were collected on standardized forms and included the numbers of postal employees screened and offered antibiotic prophylaxis, as well as the numbers of patients seen per worker hour by various medical professionals . RESULTS: One hundred members of 5 disaster medical assistance teams and other health professionals were deployed to New York City within 18 hours of activation . Over a 68-hour period, 7,076 patients were evaluated, representing all postal employees in the 6 major postal facilities in New York believed to be at risk for anthrax exposure . Of the total, 2,452 patients were seen during the first 24 hours, 3,875 during the second 24 hours, and the remaining 749 during the last 20 hours of operations . An average of 161 employees were screened per hour . The antibiotic most commonly dispensed was ciprofloxacin, followed by doxycycline and amoxicillin . CONCLUSION: The deployment of disaster medical assistance teams and other agencies to New York City to provide prophylaxis against inhalation anthrax to US Postal Service employees provides lessons for a rapid, efficient, and effective response to acts of bioterrorism . This deployment might also serve as a scaleable model for future events requiring medical prophylaxis.

Proc Natl Acad Sci U S A, 2003 Apr 1, 100(7), 4346 - 51 Epub 2003 Mar 21.
Emergency response to an anthrax attack; Wein LM et al.; We developed a mathematical model to compare various emergency responses in the event of an airborne anthrax attack . The system consists of an atmospheric dispersion model, an age-dependent dose-response model, a disease progression model, and a set of spatially distributed two-stage queueing systems consisting of antibiotic distribution and hospital care . Our results underscore the need for the extremely aggressive and timely use of oral antibiotics by all asymptomatics in the exposure region, distributed either preattack or by nonprofessionals postattack, and the creation of surge capacity for supportive hospital care via expanded training of nonemergency care workers at the local level and the use of federal and military resources and nationwide medical volunteers . The use of prioritization (based on disease stage andor age) at both queues, and the development and deployment of modestly rapid and sensitive biosensors, while helpful, produce only second-order improvements.

J Ethnopharmacol, 2003 Apr, 85(2-3), 269 - 77
Medicinal use and social status of the soap berry endod (Phytolacca dodecandra) in Ethiopia; Esser KB et al.; Berries from Phytolacca dodecandra L'Herit . (endod in Amharic) offer a readily available molluscicide to control schistosomiasis . Parts of the endod plant have been used as a detergent and as traditional medicine for centuries in Ethiopia . An interview survey was performed in the highlands of Ethiopia to provide information on the distribution of the plant, people's traditional use of it, their perception of the plant, and the potential for increased production and use of endod as a soap for indirect control of schistosomiasis . People of all ages report that they are familiar with the plant and its detergent and medicinal uses . The plant is largely disappearing from unprotected areas due to land clearing . Younger people appear to use endod as a soap whenever it is available . Older women prefer commercial soap and consider endod to be associated with poor people . Common medicinal uses include treatment of skin itching (ringworm), abortion, gonorrhea, leeches, intestinal worms, anthrax and rabies . Two thirds of the people express interest in cultivating endod for personal use if supplied with rooted cuttings . Increased cultivation of endod and use of berries for washing might be possible if information about schistosomiasis and its control is disseminated among people . Preference for commercial soap and lack of land for cultivation are major obstacles for increasing the availability and use of endod.

Vaccine, 2003 Apr 2, 21(15), 1620 - 8
Comprehensive systematic surveillance for adverse effects of anthrax vaccine adsorbed, US Armed Forces, 1998-2000; Lange JL et al.; Routine vaccinations of US military personnel with Anthrax Vaccine Adsorbed began in 1998 . To systematically identify clinical diagnoses reported more frequently after vaccination than before, all military personnel were retrospectively assigned to pre- or post-vaccination cohorts . Cohort assignments were based on vaccination statuses each day of the 3-year surveillance period . For each cohort, rates of hospitalizations and ambulatory visits for 843 specific diagnoses were calculated using data in a public health surveillance system . Compared to the pre-vaccination cohort, the post-vaccination cohort had statistically higher rates of hospitalizations for 17 diagnoses, of ambulatory visits for 34 diagnoses, and in both clinical settings for one diagnosis (malaria) . After accounting for systematic differences in coding/reporting and residual confounding, the number and nature of clinical diagnoses more frequent after anthrax vaccination than before were consistent with expectations due to random variation . This surveillance suggests that Anthrax Vaccine Adsorbed has few, if any, clinically significant adverse effects.

East Afr Med J, 2002 Jul, 79(7), 364 - 7
Anthrax revisited; Bhatt KM et al.; BACKGROUND: Anthrax is an ancient disease affecting animals and humans . Sporadic cases of anthrax and small epidemics have been seen from time to time in different parts of the world and in Africa . However many clinicians are not very familiar with the various presentations and management of anthrax . It is relevant for the health care workers to re-familiarise themselves with all aspects of anthrax, with the impending threat of bioterrorism . OBJECTIVE: To familiarise healthcare workers on all aspects of anthrax . STUDY SELECTION: To describe epidemiology pathogenesis, clinical features, management and prevention of anthrax including measures to take when weapons grade anthrax is suspected . DATA SYNTHESIS: Three forms of the disease are recognised, cutaneous, inhalational and intestinal . Cutaneous anthrax is the most common form . Inhalation anthrax is the most severe form of anthrax . The treatment of anthrax in most cases is penicillin, however with the threat of bioterrorism, intentional releases of anthrax spores in the environment has caused much concern . Weapons grade anthrax of more virulent strain and resistant to commonly used antibiotics is possible . CONCLUSION: In view of the different clinical presentations and outcomes it is important that health care workers re-familiarise themselves with the disease and in the event of bioterrorism are able to take appropriate measures.

Euro Surveill, 2002 May, 7(5), 78 - 84
Roles and functions of a European Union Public Health Centre for Communicable Diseases and other threats to health; Van Loock F et al.; An international consensus has been reached that a European Union (EU) Technical Coordination Structure (TCS) for communicable diseases is needed to improve Europe s future response to international communicable disease threats within and beyond its boundaries . After the American events of September 11 2001 and the deliberate releases of anthrax, the EU created a Health Security Committee, adopted a civil protection decision, and established for 18 months a team to develop responses for deliberate releases of biological and chemical agents . These two initiatives, the network s approach and health security work, must converge into a single stream addressing health protection for the people of Europe . They could be combined into a European Centre for Communicable Diseases that is planned to become active by 2005.

Prehospital Disaster Med, 2002 Jul-Sep, 17(3), 119 - 25
Instrument development and evaluation of domestic preparedness training for first responders; Beaton RD et al.; INTRODUCTION: In the wake of domestic terrorists attacks on 11 September 2001 and subsequent bioterrorist events employing anthrax, there no longer can be any debate about the potential for attacks employing Nuclear, Biological, or Chemical (NBC)/Weapons of Mass Destruction (WMD) . As one way of acknowledging this long-standing threat and, in a concerted effort to mitigate the effects of possible future domestic NBC/WMD terrorist attacks, the US Department of Defense (DOD) and other US governmental agencies already had mounted an effort to provide Domestic Preparedness Training for First Responders in urban centers throughout the USA . METHODS: A paper and pencil questionnaire specifically designed to evaluate the effectiveness of Domestic Preparedness Training for Emergency First Responders has been developed . An earlier version of this instrument was piloted with a convenience sample of firefighters and paramedics (n = 78) in a northwest state . Based on replies to the pilot questionnaire, a pool of 27 items based on the objectives and content of the NBC/WMD Domestic Preparedness Awareness and Operations courses (plus additional background and appraised competency items) were selected for inclusion in a Domestic Preparedness Questionnaire (DPQ) . RESULTS: This paper first describes the essential psychometric properties of the DPQ based on replies from baseline and follow-up samples (n = 206 and n = 246 respectively) of urban firefighters and paramedics employed by a metropolitan city in a northwest state . The DPQ was employed to evaluate the outcomes of Domestic Preparedness training provided to a sample of urban fire-service personnel . The DPQ documented significant improvements in a group of "DP trained"-urban firefighters (n = 80) both in their awareness and operations content knowledge as well as in their perceived competencies to respond to acts of biological, chemical, or nuclear terrorism "in their own community" at four months post-training . A comparison group of "Not DP-trained" firefighters (n = 78) showed no statistically significant changes on these DPQ indices, suggesting that the documented improvements in the "DP-trained" firefighters on the DPQ were not due to "test reactivity" or to "historical" factors . CONCLUSION: The findings suggest that the DPQ has adequate inter-item and test-retest reliability, possesses concurrent validity, and appears to be a sensitive measure of the Domestic Preparedness Training provided for urban firefighter and paramedic First Responders.

Account Res, 2002 Apr-Jun, 9(2), 93 - 103
Informed consent and investigational new drug abuses in the U.S . military; Cummings ML; Objective: The focal point of this investigation was to research the ethical issues surrounding the military's requests for informed consent waivers when using investigational drugs, and the recent debate surrounding the anthrax vaccine as an investigational new drug (IND) . Design: The military's management of the informed consent process was examined using documents obtained through the Freedom of Information Act, Institutional Review Board (IRB) minutes, legal pleadings, and protocols for specific investigational drugs . Results: In December 1990, prior to Operation Desert Storm, the Federal Drug Administration (FDA) granted the Department of Defense (DoD) an unprecedented waiver to the federally mandated informed-consent requirement for the use of investigational drugs . However, the waiver approval was conditional, and the FDA insisted on several safeguards . Partially in response to the subsequent Gulf War Syndrome debate, the FDA recently evaluated the military's use of investigational drugs during the Gulf War . The FDA cited the military for significant deviations from the originally approved protocols . Most notably, the military was found to be abusing the IRB process by convening a second IRB when the first IRB concluded that waiving informed consent was unethical . In addition, there was a gross lack of documentation and no monitoring of adverse reactions . The DoD's plan to use the current anthrax vaccine on all 2.4 million troops against inhalation anthrax has kindled an additional investigational drug controversy . The safety and efficacy of the use of the anthrax vaccine as a prophylactic against inhalation anthrax have been questioned by both military and medical organizations . There have never been any published studies of human efficacy or long-term effects for the anthrax vaccine . In addition, the military is not using the vaccine for its intended purpose, and it is also not adhering to prescribed dosing schedules . There is clear evidence to support the claim that, in fact, the military's use of the anthrax vaccine should be considered unethical . Conclusions: I argue that in medical situations, the military is obligated to treat its troops as autonomous persons entitled to basic rights and protections . The DoD is currently using an approved drug, the anthrax vaccine, for an unapproved purpose and in an unapproved manner . In doing so, the DoD is not only violating the FDA's regulations against such practices, it is also violating an executive order which only allows the president to authorize the use of INDs on service members without their consent.

Vaccine, 2003 Mar 28, 21(13-14), 1348 - 54
Adverse medical events in British service personnel following anthrax vaccination; Enstone JE et al.; The safety of the UK anthrax vaccine in British service personnel was evaluated by a retrospective cohort study of randomly selected personnel from five Royal Air Force bases by investigating adverse medical events and consultation rates for a period before and after vaccination . Vaccination acceptance rate varied from 27 to 89% (P=0.0001) . In the vaccinated cohort 11.1% (n=368) reported side-effects . The number of consultations in the year prior to vaccination (P=0.04) and RAF base (P=0.0085) were associated with side-effects . Only the RAF base remained a statistically significant factor (P=0.007) after adjusting for other factors . The anthrax vaccine resulted in mild side-effects in 11%, and no serious side-effects were observed . Acceptors of vaccine did not have significantly more medical consultations following vaccination than their unvaccinated counterparts.

Antiviral Res, 2003 Jan, 57(1-2), 7 - 12
Smallpox: a potential agent of bioterrorism; Whitley RJ; The events of 11 September 2001, in New York City, and subsequent identification of anthrax in the United States Postal System, have generated a new sense of awareness for the potential of biological terrorism, if not warfare . Among those agents identified by the Centers for Disease Control and Prevention as 'Class A Bioterrorist Threats', smallpox is among the most dangerous . The ease of transmission of this agent, the lack of immunity in the population at large to this agent, and rapidity of its spread, if released, all generate significant concern for its deployment . A vaccine directed against smallpox is available but it is also associated with significant adverse events-some of which are life-threatening . Further, no antiviral drug has proven efficacious for therapy of human disease, although one licensed drug, cidofovir, does have in vitro activity . Regardless, heightened awareness should lead to the development of a vaccine without significant adverse events and safe and efficacious antiviral drugs . The availability of a vaccine and antiviral drugs that are safe would significantly remove any major threat of smallpox deployment by a terrorist.

Microbes Infect, 2003 Jan, 5(1), 69 - 74
Robert Koch; Munch R; This article traces the origins of bacteriological research, with particular attention to the role of Robert Koch, and his postulates, on infectious agents . By chronologically following Koch's work on anthrax, germ photography and tuberculosis, it shows how the visual representation of germs transformed laboratory research in medical science.

Schweiz Arch Tierheilkd, 2003 Jan, 145(1), 7 - 16
{Sacer ignis, quam pustulam vocant pastores: anthrax--cultural historical traces of a zoonosis}; Eitel J; The knowledge of anthrax as a disease and its importance as a zoonosis in the Greco-Roman world is revealed through a selection of classical texts and mythological sources, taking into account evidence of reworking and reuse of these texts up until the nineteenth century . The numerous names given to the disease throughout history and their linguistic origins will also be examined in this paper . The narrative of the epizoonoses in Noricum in Virgil's Georgics; taken by several to represent a description of an anthrax epidemic, and which had a great influence in written works on veterinary medicine up until the discovery of bacteria, will be given particular attention . The crucial term is "Sacer Ignis", synonymous for several different human and animal diseases through time . This term will be analysed in terms of linguistic origin and the changes in meaning it acquired throughout the centuries.

Am J Clin Pathol, 2003 Feb, 119(2), 292 - 7
Effects of sterilizing gamma irradiation on bloodspot newborn screening tests and whole blood cyclosporine and tacrolimus measurements; Stickle DF et al.; Sterilizing irradiation of the US mail has been proposed as a method to prevent delivery of viable anthrax spores . Because newborn screening samples (bloodspots) and cyclosporine and tacrolimus specimens (whole blood) are delivered routinely through the mail, we studied whether sterilizing gamma irradiation could affect these test results . Specimens were exposed to 18 kGy gamma irradiation (100 hours x 18,000 rad/h), a "kill dose" for Bacillus pumilus spore strips . Irradiation had no significant effect on whole blood cyclosporine or tacrolimus results, but it had a degradative effect on bloodspot phenylalanine, hemoglobins, biotinidase, galactose-1-phosphate uridyltransferase, thyroxine, and thyrotropin . Such irradiation potentially could cause false-negative results for the detection of phenylketonuria and likely would lead to an increase in secondary testing for hemoglobin variants, but it is unlikely to lead to false-negative or false-positive results for the remaining newborn screening tests . These experiments cannot rule out possible greater effects by larger doses or other types of irradiation.

Curr Med Chem, 2003 Jan, 10(1), 21 - 39
Biological activity and synthetic metodologies for the preparation of fluoroquinolones, a class of potent antibacterial agents; Da Silva AD et al.; In this present review we report different synthetic methodologies for the preparation of fluoroquinolones and their biological properties . The appearance of the fluoroquinolones, a new class of antibacterial agents (based on nalidixic acid, 4-quinolone-3-carboxylates), in early 1980's, gave a new impulse for the international competition to synthesize more effective drugs . Fluoroquinolones have a broad spectrum of activity against Gram-positive, Gram-negative and mycobacterial organisms as well as anaerobes . The fluoroquinolone ciprofloxacin hydrochloride is an important bioterrorist weapon and also an antibiotic used to treat bacterial infection in many different parts of the body, approved for use in patients who have been exposed to the inhaled form of anthrax.

J Cell Biol, 2003 Feb 3, 160(3), 295 - 6
Anthrax toxin rafts into cells; Kurzchalia T; Anthrax toxin binds to a plasma membrane receptor and after endocytosis exerts its deadly effects on the cell . Until now, however, the mechanism of initial toxin uptake was unknown . In this issue, Abrami et al . (2003) demonstrate that toxin oligomerization clusters the anthrax receptor into lipid rafts and this complex is internalized via the clathrin-dependent pathway.

Am J Emerg Med, 2003 Jan, 21(1), 77 - 9
Meeting the challenge of bioterrorism: lessons learned from West Nile virus and anthrax; Crupi RS et al.; Hospital emergency departments (EDs) and ambulatory clinics may be the first to recognize illness related to a bioterrorist event . Every health-care institution must develop a weapons-of-mass- destruction (WMD) preparedness plan as part of its all-hazards disaster planning . As part of an all-hazards disaster plan, WMD preparedness should use the incident-command model to insure the required chain of command for effectively coordinating activities between hospital departments and external agencies . Preparedness for bioterrorism poses unique challenges . In the event of a biological attack, the hospital infection control staff and administration must already have in place the means to communicate with local and state public health agencies, the Centers for Disease Control and Prevention (CDC), local law-enforcement agencies, and the Federal Bureau of Investigation (FBI) . Local and regional planners must consider how to coordinate the responses of emergency medical services (EMS), police, and fire departments with healthcare providers and the news media . Most hospitals are ill equipped to deal with a catastrophic event caused by WMD . The burden of responding to such events will fall initially on ED physicians and staff members . The severity of such an incident might be mitigated with careful planning, training and education . The responses of one hospital network to the outbreak of West Nile virus and, more recently, to the threat of anthrax, are presented as guides for bioterrorism preparedness .

J Cell Biol, 2003 Feb 3, 160(3), 321 - 8 Epub 2003 Jan 27.
Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process; Abrami L et al.; The protective antigen (PA) of the anthrax toxin binds to a cell surface receptor and thereby allows lethal factor (LF) to be taken up and exert its toxic effect in the cytoplasm . Here, we report that clustering of the anthrax toxin receptor (ATR) with heptameric PA or with an antibody sandwich causes its association to specialized cholesterol and glycosphingolipid-rich microdomains of the plasma membrane (lipid rafts) . We find that although endocytosis of ATR is slow, clustering it into rafts either via PA heptamerization or using an antibody sandwich is necessary and sufficient to trigger efficient internalization and allow delivery of LF to the cytoplasm . Importantly, altering raft integrity using drugs prevented LF delivery and cleavage of cytosolic MAPK kinases, suggesting that lipid rafts could be therapeutic targets for drugs against anthrax . Moreover, we show that internalization of PA is dynamin and Eps15 dependent, indicating that the clathrin-dependent pathway is the major route of anthrax toxin entry into the cell . The present work illustrates that although the physiological role of the ATR is unknown, its trafficking properties, i.e., slow endocytosis as a monomer and rapid clathrin-mediated uptake on clustering, make it an ideal anthrax toxin receptor.

Ann Pharmacother, 2003 Feb, 37(2), 297 - 300
Figs--the earliest known ancient drug for cutaneous anthrax; Ben-Noun LL; BACKGROUND: Anthrax is an often fatal bacterial infection, occurring in cutaneous, inhalational, gastrointestinal, and meningeal forms . Evaluation of anthrax treatment from ancient history may help healthcare providers to handle this serious disease more efficiently . OBJECTIVE: To evaluate the biblical descriptions of anthrax, focusing on its therapy in ancient times . STUDY SELECTION: All biblical texts associated with anthrax were examined and passages relating to this disease were studied closely . DATA SYNTHESIS: Biblical passages such as: "Take a cluster of figs . And they took and laid it on the boil {anthrax}, and he recovered," and "Let them take a cluster of figs, and lay it upon the boil {anthrax}, and he shall recover," convincingly indicate that figs have healing properties in cutaneous anthrax lesions . CONCLUSIONS: On the basis of this study, the National Institutes of Health together with the pharmaceutical industry may consider to work on isolation of compounds from fig plants to develop products against cutaneous and possibly other forms of anthrax once screening tests are completed.

BMC Med Inform Decis Mak . 2003 Jan 23;3(1):2.
Time series modeling for syndromic surveillance; Reis BY et al.; BACKGROUND: Emergency department (ED) based syndromic surveillance systems identify abnormally high visit rates that may be an early signal of a bioterrorist attack . For example, an anthrax outbreak might first be detectable as an unusual increase in the number of patients reporting to the ED with respiratory symptoms . Reliably identifying these abnormal visit patterns requires a good understanding of the normal patterns of healthcare usage . Unfortunately, systematic methods for determining the expected number of (ED) visits on a particular day have not yet been well established . We present here a generalized methodology for developing models of expected ED visit rates . METHODS: Using time-series methods, we developed robust models of ED utilization for the purpose of defining expected visit rates . The models were based on nearly a decade of historical data at a major metropolitan academic, tertiary care pediatric emergency department . The historical data were fit using trimmed-mean seasonal models, and additional models were fit with autoregressive integrated moving average (ARIMA) residuals to account for recent trends in the data . The detection capabilities of the model were tested with simulated outbreaks . RESULTS: Models were built both for overall visits and for respiratory-related visits, classified according to the chief complaint recorded at the beginning of each visit . The mean absolute percentage error of the ARIMA models was 9.37% for overall visits and 27.54% for respiratory visits . A simple detection system based on the ARIMA model of overall visits was able to detect 7-day-long simulated outbreaks of 30 visits per day with 100% sensitivity and 97% specificity . Sensitivity decreased with outbreak size, dropping to 94% for outbreaks of 20 visits per day, and 57% for 10 visits per day, all while maintaining a 97% benchmark specificity . CONCLUSIONS: Time series methods applied to historical ED utilization data are an important tool for syndromic surveillance . Accurate forecasting of emergency department total utilization as well as the rates of particular syndromes is possible . The multiple models in the system account for both long-term and recent trends, and an integrated alarms strategy combining these two perspectives may provide a more complete picture to public health authorities . The systematic methodology described here can be generalized to other healthcare settings to develop automated surveillance systems capable of detecting anomalies in disease patterns and healthcare utilization.

Eur J Biochem, 2003 Feb, 270(3), 404 - 14
Novel aspects of calmodulin target recognition and activation; Vetter SW et al.; Several crystal and NMR structures of calmodulin (CaM) in complex with fragments derived from CaM-regulated proteins have been reported recently and reveal novel ways for CaM to interact with its targets . This review will discuss and compare features of the interaction between CaM and its target domains derived from the plasma membrane Ca2+-pump, the Ca2+-activated K+-channel, the Ca2+/CaM-dependent kinase kinase and the anthrax exotoxin . Unexpected aspects of CaM/target interaction observed in these complexes include: (a) binding of the Ca2+-pump domain to only the C-terminal part of CaM (b) dimer formation with fragments of the K+-channel (c) insertion of CaM between two domains of the anthrax exotoxin (d) binding of Ca2+ ions to only one EF-hand pair and (e) binding of CaM in an extended conformation to some of its targets . The mode of interaction between CaM and these targets differs from binding conformations previously observed between CaM and peptides derived from myosin light chain kinase (MLCK) and CaM-dependent kinase IIalpha (CaMKIIalpha) . In the latter complexes, CaM engulfs the CaM-binding domain peptide with its two Ca2+-binding lobes and forms a compact, ellipsoid-like complex . In the early 1990s, a model for the activation of CaM-regulated proteins was developed based on this observation and postulated activation through the displacement of an autoinhibitory or regulatory domain from the target protein upon binding of CaM . The novel structures of CaM-target complexes discussed here demonstrate that this mechanism of activation may be less general than previously believed and seems to be not valid for the anthrax exotoxin, the CaM-regulated K+-channel and possibly also not for the Ca2+-pump.

Clin Infect Dis, 2003 Feb 1, 36(3), 328 - 36 Epub 2003 Jan 20.
Clinical features that discriminate inhalational anthrax from other acute respiratory illnesses; Kuehnert MJ et al.; Inhalational anthrax (IA) is a rapidly progressive disease that frequently results in sepsis and death, and prompt recognition is critical . To distinguish IA from other causes of acute respiratory illness, patients who had IA were compared with patients in an ambulatory clinic who had influenza-like illness (ILI) and with hospitalized patients who had community-acquired pneumonia (CAP) at the initial health care visit . Compared with patients who had ILI, patients who had IA were more likely to have tachycardia, high hematocrit, and low albumin and sodium levels and were less likely to have myalgias, headache, and nasal symptoms . Scoring systems were devised to compare IA with ILI or CAP on the basis of strength of association . For ILI, a score of > or =4 captured all 11 patients with IA and excluded 664 (96.1%) of 691 patients with ILI . Compared with patients who had CAP, patients with IA were more likely to have nausea or vomiting, tachycardia, high transaminase levels, low sodium levels, and normal white blood cell counts . For CAP, a score of > or =3 captured 9 (81.8%) of 11 patients with IA and excluded 528 (81.2%) of 650 patients with CAP . In conclusion, selected clinical features of patients with IA differ from those of patients with ILI and are more similar to those of patients with CAP.

Mod Healthc, 2002 Dec 23-30, 32(51), 22 - 4
Year in review 2002; Moon S; The year opened on a somber note, with the nation still struggling to cope with the aftermath of the Sept . 11, 2001, attacks and subsequent anthrax scare . The healthcare industry was scrambling to be ready for any future attacks and pondering the best preparedness measures . Meanwhile, compliance and quality of care simmered on the back burner, along with soaring malpractice insurance costs and growing budget deficits in the states . And debate over provider reimbursement rates, staffing shortages and more double-digit increases in the cost of healthcare coverage also made headlines.

Proc Natl Acad Sci U S A, 2003 Jan 21, 100(2), 657 - 62 Epub 2003 Jan 13.
Potent antitumor activity of a urokinase-activated engineered anthrax toxin; Liu S et al.; The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy . We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity . Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage . Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice . In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice . Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase . The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors . This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation . The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.

Gesundheitswesen, 2002 Dec, 64(12), 689 - 91
{Consequences and challenges due to bioterrorist attacks}; Kurth R; Ever since the terrorist attacks of 11 September 2001 and the cases of inhalational anthrax and other types of anthrax caused by attacks with anthrax spores, responsible authorities and experts must reckon with bioterrorist attacks conducted with much greater criminal "drive" and greater financial resources than had been imagined so far . This consideration triggered cautionary measures in Germany and Europe as briefly summarised here . For more detailed information please refer to internet and see the references given below.

Qual Manag Health Care, 2002 Spring, 10(3), 31 - 9
Anthrax attacks and practice patterns: a learning opportunity for health care systems; Jones JW et al.; Sudden and unexpected events directly influencing clinical practice patterns are uncommon . After the first report of bioterrorism-related anthrax, the authors studied retrospectively 13 months of anthrax-related antibiotic prescription rates for Veterans Affairs outpatients in one urban area where no cases of anthrax were reported . During the 26 days after the first anthrax report, the rate of acute respiratory illnesses treated with fluoroquinolones was 62.8 per 10,000 outpatient visits, an increase of 41 percent over the rate of 44.4 observed approximately one year earlier (p = 0.058) . Acute sociopolitical events such as bioterrorist attacks present a unique opportunity to investigate changes in health care.

J Community Health Nurs, 2002 Winter, 19(4), 203 - 11
Bioterrorism preparedness for local health departments; Morse A; Bioterrorism preparedness has not traditionally been an everyday concern of local public health departments . The likely first responders to a biological bioterrorism event will be local public health personnel . The events of September 11, 2001, and the anthrax crisis that followed tested the capabilities of the public health system and demonstrated its fragility . Little federal funding has trickled down to local health departments, and they have not been included in planning or training for bioterrorism preparedness . Now local health departments must develop detailed bioterrorism response plans . Effective plans will involve internal assessment of strengths and weaknesses and strategizing with other local community agencies . Our health department is a suburban county agency that serves a population of over 250,000 . We have started this self-assessment and planning process . This bioterrorism guide has provided some structure for us and may be helpful for other local health departments as they begin this process.

Semin Pediatr Infect Dis, 2002 Oct, 13(4), 289 - 99
Robert Koch: Nobel laureate and controversial figure in tuberculin research; Ligon BL; Tuberculosis has been a major cause of death for centuries . Likewise, anthrax has posed a deadly threat to both farm animals and humans and today poses a threat as a weapon of biological warfare . Cholera, which wreaked havoc in the East and threatened to enter Europe, also posed a deadly threat . The causes of these diseases remained mysteries for centuries . Nobel laureate Robert Koch (1843-1910), often called the founder of medical bacteriology, is credited with discovering the tubercle bacillus, Mycobacterium tuberculosis; with demonstrating for the first time in history the life cycle of the anthrax bacillus under controlled in vitro conditions; and with identifying Vibrio cholorae as the cause of cholera . In later life, he also was at the center of several controversies . This article provides a brief summary of Koch's exploration into bacteriology and, especially, his experience with tuberculosis and the controversies that developed in the latter part of his life, as well as his childhood and early adult years and the development of his now well-known "postulates."

EMBO J, 2002 Dec 16, 21(24), 6721 - 32
Physiological calcium concentrations regulate calmodulin binding and catalysis of adenylyl cyclase exotoxins; Shen Y et al.; Edema factor (EF) and CyaA are calmodulin (CaM)-activated adenylyl cyclase exotoxins involved in the pathogenesis of anthrax and whooping cough, respectively . Using spectroscopic, enzyme kinetic and surface plasmon resonance spectroscopy analyses, we show that low Ca(2+) concentrations increase the affinity of CaM for EF and CyaA causing their activation, but higher Ca(2+) concentrations directly inhibit catalysis . Both events occur in a physiologically relevant range of Ca(2+) concentrations . Despite the similarity in Ca(2+) sensitivity, EF and CyaA have substantial differences in CaM binding and activation . CyaA has 100-fold higher affinity for CaM than EF . CaM has N- and C-terminal globular domains, each binding two Ca(2+) ions . CyaA can be fully activated by CaM mutants with one defective C-terminal Ca(2+)-binding site or by either terminal domain of CaM while EF cannot . EF consists of a catalytic core and a helical domain, and both are required for CaM activation of EF . Mutations that decrease the interaction of the helical domain with the catalytic core create an enzyme with higher sensitivity to Ca(2+)-CaM activation . However, CyaA is fully activated by CaM without the domain corresponding to the helical domain of EF.

Biochem Biophys Res Commun, 2003 Jan 3, 300(1), 61 - 4
Exchange characteristics of calcium ions bound to anthrax protective antigen; Gao-Sheridan S et al.; Protective antigen (PA), the receptor-binding moiety of anthrax toxin, contains two calcium atoms buried within domain 1(') (amino acid residues 168-258) . We showed that these ions are stably bound and exchange with free 45Ca(2+) only slowly (t(1/2) approximately 4.0 h) . Dissociation is the rate-limiting step . PA(63), the heptameric prepore form of PA, showed a slightly higher exchange rate than the monomeric intact protein . Exchange by this form was retarded by binding of the enzymatic moieties of the toxin, but was unaffected by reducing the pH to 5.0, a condition known to trigger conversion of the prepore to the pore form . These results are consistent with the hypothesis that bound Ca(2+) within PA plays primarily a structural role, maintaining domain 1(') in a conformation that allows PA(63) to oligomerize and bind the enzymatic moieties of the toxin.

J Biol Chem, 2003 Feb 14, 278(7), 5227 - 34 Epub 2002 Dec 04.
Cell surface tumor endothelium marker 8 cytoplasmic tail-independent anthrax toxin binding, proteolytic processing, oligomer formation, and internalization; Liu S et al.; The interaction of anthrax toxin protective antigen (PA) and target cells was assessed, and the importance of the cytosolic domain of tumor endothelium marker 8 (TEM8) in its function as a cellular receptor for PA was evaluated . PA binding and proteolytic processing on the Chinese hamster ovary cell surface occurred rapidly, with both processes nearly reaching steady state in 5 min . Remarkably, the resulting PA63 fragment was present on the cell surface only as an oligomer, and furthermore, the oligomer was the only PA species internalized, suggesting that oligomerization of PA63 triggers receptor-mediated endocytosis . Following internalization, the PA63 oligomer was rapidly and irreversibly transformed to an SDS/heat-resistant form, in a process requiring an acidic compartment . This conformational change was functionally correlated with membrane insertion, channel formation, and translocation of lethal factor into the cytosol . To explore the role of the TEM8 cytosolic tail, a series of truncated TEM8 mutants was transfected into a PA receptor-deficient Chinese hamster ovary cell line . Interestingly, all of the cytosolic tail truncated TEM8 mutants functioned as PA receptors, as determined by PA binding, processing, oligomer formation, and translocation of an lethal factor fusion toxin into the cytosol . Moreover, cells transfected with a TEM8 construct truncated before the predicted transmembrane domain failed to bind PA, demonstrating that residues 321-343 are needed for cell surface anchoring . Further evidence that the cytosolic domain plays no essential role in anthrax toxin action was obtained by showing that TEM8 anchored by a glycosylphosphatidylinositol tail also functioned as a PA receptor.

Proc AMIA Symp . 2002;:365-91.
National Pharmaceutical Stockpile drill analysis using XML data collection on wireless Java phones; Karras BT et al.; This study describes an informatics effort to track subjects through a National Pharmaceutical Stockpile (NPS) distribution drill . The drill took place in Seattle on 1/24/2002 . Washington and the State Department of Health are among the first in the nation to stage a NPS drill testing the distribution of medications to mock patients, thereby testing the treatment capacity of the plan given a post-anthrax exposure scenario . The goal of the Public Health Informatics Group at the University of Washington was to use informatics approaches to monitor subject numbers and elapsed time . This study compares accuracy of time measurements using a mobile phone Java application to traditional paper recording in a live drill of the NPS . Pearson correlation = 1.0 in 2 of 3 stations . Differences in last station measurements can be explained by delay in recording of the exit time . We discuss development of the application itself and lessons learned . (MeSH Bioterrorism, Informatics, Public Health)

Hong Kong Med J, 2002 Dec, 8(6), 440 - 6
Hospital preparedness for chemical and biological incidents in Hong Kong; Chan JT et al.; The risk of mass exposure to toxic substances has increased steadily during the twentieth century due to the expansion of industry and the deliberate development and use of agents of chemical warfare . Although Hong Kong is considered a relatively safe place, hoax anthrax attacks have occurred since 17 October 2001 . People who have been seriously injured by hazardous materials have a greater chance of recovery without complications when appropriate emergency treatments are provided . Recognition and identification of hazardous materials, assessment of the conditions, decontamination, and protection of staff and facilities are important elements in the formulation of a contingency plan . The objective of this article is to outline the efforts of the Hong Kong Hospital Authority in formulating a hospital response to incidents involving hazardous materials.

Vaccine, 2002 Dec 13, 21(3-4), 211 - 20
Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by immunization with dendritic cells transduced with replication-defective recombinant adenovirus; Matsui M et al.; We studied the potential of dendritic cells (DCs) in priming hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTLs) in mice . Recombinant adenovirus expressing HCV core (Adex1SR3ST) was employed to express core in DCs . Core-specific CTLs are effectively elicited by injecting Adex1SR3ST-transduced DCs, whereas injection of Adex1SR3ST does not result in effective priming . Further, Adex1SR3ST-transduced DCs more efficiently prime core-specific CTLs than Adex1SR3ST-transduced macrophages, or DCs treated with an anthrax toxin fusion protein reported previously . Upon challenge with recombinant HCV-core-expressing vaccinia virus, vaccinia titers are significantly reduced in mice immunized with Adex1SR3ST-transduced DCs . Thus, adenovirus-transduced DCs may be a promising candidate for a CTL-based vaccine against HCV.

Health Aff (Millwood), 2002 Nov-Dec, 21(6), 117 - 30
Public health and national security: the critical role of increased federal support; Frist B; Protecting the public's health historically has been a state and local responsibility . However, the growing threat of bioterrorism has highlighted the importance of a strong public health infrastructure to the nation's homeland security and has focused increased attention on the preparedness of the public health system . As a result, federal public health funding has increased exponentially since the anthrax attacks of late 2001, and Congress has passed sweeping new federal legislation intended to strengthen the nation's public health system . This heightened level of federal interest and support should yield important public health benefits . Most recognize that after years of neglect the public health infrastructure cannot be rebuilt overnight . As we implement a comprehensive strategy to increase the capabilities and capacity of our nation's public health system, it is essential to address a series of important policy questions, including the appropriate level of ongoing public health investments from local, state, and federal sources.

Health Aff (Millwood), 2002 Nov-Dec, 21(6), 106 - 16
Dealing with the dangers of fear: the role of risk communication; Gray GM et al.; Among the many lessons of the homeland terrorist attacks of 2001 was that fear has powerful public health implications . People chose to drive instead of flying, thereby raising their risk of injury or death . Thousands took broad-spectrum antibiotics to prevent possible anthrax infections, thereby accelerating antimicrobial resistance . Such potentially harmful actions were taken by people seeking a sense of safety because they were afraid . This essay argues for greater emphasis on risk communication to help people keep their fears in perspective . Effective communication, not only through what the government says but implicit in the actions it takes, empowers people to make wiser choices in their own lives, and to support wise choices by society in applying limited resources to maximize public and environmental health.

Vet Clin North Am Food Anim Pract, 2002 Nov, 18(3), 379 - 87, v
Maintaining a vigilance for foreign animal diseases; Waldrup KA et al.; The incursion of foot-and-mouth disease (FMD) into the United Kingdom in February 2001 served as a wakeup call for North American agriculture . As the livestock health crisis in the United Kingdom progressed, it became increasingly evident that the United States, Canada, and Mexico were also susceptible to an incursion of a foreign animal disease . The terrorist attacks of September 11, 2001, and the subsequent anthrax mailings reaffirmed the fact that the United States is vulnerable to an infectious assault, regardless of whether it is intentional or accidental.

J Med Microbiol, 2002 Oct, 51(10), 821 - 31
In-vitro characterisation of the phagocytosis and fate of anthrax spores in macrophages and the effects of anti-PA antibody; Welkos S et al.; Antibodies (Abs) to the protective antigen (PA) component of the anthrax toxins have anti-spore as well as anti-toxin activities . Anti-PA antisera and purified anti-PA Abs enhance the phagocytosis by murine-derived macrophages (MQs) of spores of the Ames and Sterne strains and retard the germination of extracellular spores in vitro . The fate after phagocytosis of untreated and anti-PA-treated spores was further studied in culture medium that supported phagocytosis without stimulating spore germination (Dulbecco's minimal essential medium with horse serum 10%) . The spores germinated within cells of primary peritoneal murine MQs (C3H/HeN) and MQs of the RAW264.7 MQ-like cell line; germination was associated with a rapid decline in spore viability . Exposure of MQs to inhibitors of phago-endosomal acidification (bafilomycin A and chloroquine) reduced the efficiency of MQ killing and allowed outgrowth and replication of the organisms . Treatment of spores with anti-PA Abs stimulated their phagocytosis and was associated with enhanced MQ killing of the spores . The enhanced killing of spores correlated with the greater extent of germination of anti-PA-treated spores after phagocytosis . A PA null mutant of the Ames strain exhibited none of the effects associated with anti-PA Ab treatment ofthe parental strain . Thus, the anti-PA Ab-specific immunity induced by vaccines has anti-spore activities and its role in impeding the early stages of infection with Bacillusanthracis needs to be assessed.

Dis Mon, 2002 Aug, 48(8), 493 - 564
Biological terrorism: understanding the threat, preparation, and medical response; Franz DR et al.; The thought of an outbreak of disease caused by the intentional release of a pathogen or toxin in an American city was alien just 10 years ago . Many people believed that biological warfare was only in the military's imagination, perhaps to be faced by soldiers on a far-away battlefield, if at all . The "anthrax letters" and the resulting deaths from inhalation anthrax have changed that perception . The national, state, and local governments in the United States are preparing for what is now called "not if, but when and how extensive" biological terrorism . In contrast to the acute onset and first-responder focus with a chemical attack, in a bioterrorist attack, the physician and the hospital will be at the center of the fray . Whether the attack is a hoax, a small food-borne outbreak, a lethal aerosol cloud moving silently through a city at night, or the introduction of contagious disease, the physician who understands threat agent characteristics and diagnostic and treatment options and who thinks like an epidemiologist will have the greatest success in limiting the impact of the attack . As individual health care providers, we must add the exotic agents to our diagnostic differentials . Hospital administrators must consider augmenting diagnostic capabilities and surveillance programs and even making infrastructure modifications in preparation for the treatment of victims of bioterrorism . Above all, we must all educate ourselves . If done correctly, preparation for a biological attack will be as "dual use" as the facility that produced the weapon . A sound public health infrastructure, which includes all of us and our resources, will serve this nation well for the control of the disease, no matter what the cause of the disease.

Cell Cycle, 2002 Jan, 1(1), 10 - 5
Anthrax, MEK and cancer; Bodart JF et al.; The MEK family of protein kinases plays key roles in regulating cellular responses to mitogens as well as environmental stress . Inappropriate activation of these kinases contributes to tumorigenesis . In contrast, anthrax lethal factor, the principal virulence factor of anthrax toxin, has been demonstrated to selectively inactivate MEKs . In this article we will discuss recent advances in our understanding of molecular aspects of the pathogenesis of anthrax, emphasizing the potential role of MEK signalling in this disease, and outline novel strategies to use anthrax lethal toxin in the treatment of cancer.

Tijdschr Diergeneeskd, 2002 Oct 15, 127(20), 616 - 9
{Bioterrorism: the role of veterinarians in detection and prevention}; de Balogh KK et al.; The fear of terrorist attacks has increased since the events of 11 September 2001 in New York . In the weeks following the terrorist attack, letters containing anthrax spores were received at various locations in the USA . This shows that bioterrorism is possible and that is necessary to be prepared for the potential release of biological agents . Such agents can be distributed not only via the air and drinking water but also via household pets . The aim of terrorist attacks, namely, the disruption of society and daily life, can be achieved in three ways, ways which are of importance to practising veterinarians, namely, via pets, via contamination of pet foods of animal origin, and by the spread of infectious animal diseases that have far-reaching economic consequences . These ways are discussed in this article, together with possible ways in which veterinarians can act to diminish the consequences of such an event.

Physician Exec, 2002 Sep-Oct, 28(5), 64 - 6
Smallpox vaccine policy: the national debate; Benjamin GC; As a result of the 2001 anthrax attacks, the U.S . government is trying to forge a plan to handle something much worse: an outbreak of smallpox due to terrorist activity . Here's a look at where the debate stands today.

Online J Issues Nurs . 2002;7(3):5.
Public health nursing practice: aftermath of September 11, 2001; Berkowitz B; America's experience on September 11, 2001, forms the backdrop of this review of the public health nursing role in bioterrorism preparedness . The risks and challenges to the public health infrastructure are reviewed in order to place bioterrorism preparedness in a public health context . A review of the literature provides background material on the extent to which public health has evolved in planning for a bioterrorism event . The skills and competencies that will prepare public health nurses in their planning for and response to threats of bioterrorism are addressed . Anthrax is used as an example to illustrate how public health nursing can assist in a bioterrorism response.

Emerg Infect Dis, 2002 Oct, 8(10), 1160 - 2
Epidemic anthrax in the eighteenth century, the Americas; Morens DM; Anthrax has been described as a veterinary disease of minor importance to clinical medicine, causing occasional occupational infections in single cases or clusters . Its potential for rapid and widespread epidemic transmission under natural circumstances has not been widely appreciated . A little-known 1770 epidemic that killed 15,000 people in Saint-Domingue (modern Haiti) was probably intestinal anthrax . The epidemic spread rapidly throughout the colony in association with consumption of uncooked beef . Large-scale, highly fatal epidemics of anthrax may occur under unusual but natural circumstances . Historical information may not only provide important clues about epidemic development but may also raise awareness about bioterrorism potential.

Emerg Infect Dis, 2002 Oct, 8(10), 1096 - 102
Laboratory response to anthrax bioterrorism, New York City, 2001; Heller MB et al.; In October 2001, the greater New York City Metropolitan Area was the scene of a bioterrorism attack . The scale of the public response to this attack was not foreseen and threatened to overwhelm the Bioterrorism Response Laboratory's (BTRL) ability to process and test environmental samples . In a joint effort with the Centers for Disease Control and Prevention and the cooperation of the Department of Defense, a massive effort was launched to maintain and sustain the laboratory response and return test results in a timely fashion . This effort was largely successful . The development and expansion of the facility are described, as are the special needs of a BTRL . The establishment of a Laboratory Bioterrorism Command Center and protocols for sample intake, processing, reporting, security, testing, staffing, and and quality control are also described.

Emerg Infect Dis, 2002 Oct, 8(10), 1093 - 5
Coordinated response to reports of possible anthrax contamination, Idaho, 2001; Tengelsen L et al.; In 2001, the intentional release of anthrax spores in the eastern United States increased concern about exposure to anthrax nationwide, and residents of Idaho sought assistance . Response from state and local agencies was required, increasing the strain on epidemiologists, laboratorians, and communications personnel . In late 2001, Idaho's public health communications system handled 133 calls about suspicious powders . For each call, a multiagency bridge call was established, and participants (public health officials, epidemiologists, police, Federal Bureau of Investigation personnel, hazardous materials officials, and others) determined which samples would be tested by the state public health laboratory . A triage system for calls helped relieve the burden on public safety and health systems.

Harv Bus Rev, 2002 Oct, 80(10), 80 - 9, 129
Open-market innovation; Rigby D et al.; Companies in many industries are feeling immense pressure to improve their ability to innovate . Even in these tough economic times, executives have pushed innovation initiatives to the top of their priority lists, but they know that the best ideas aren't always coming out of their own R&D labs . That's why a growing number of companies are exploring the idea of open-market innovation--an approach that uses tools such as licensing, joint ventures, and strategic alliances to bring the benefits of free trade to the flow of new ideas . For instance, when faced with the unanticipated anthrax scare last fall, Pitney Bowes had nothing in its R&D pipeline to help its customers combat the deadly spores . So it sought help from outside innovators to come up with scanning and imaging technologies that could alert its customers to tainted letters and packages . And Dow Chemical and Cargill jointly produced a new form of plastic derived from plant starches--a breakthrough product that neither company could have created on its own . In this article, Bain consultants Darrell Rigby and Chris Zook describe the advantages and disadvantages of open-market innovation and the ways some companies are using it to gain competitive advantage . By importing ideas from the outside, the authors say, companies can collect more and better ideas from different kinds of experts . Creative types within a company will stick around longer if they know their ideas will eventually find a home--as internal R&D projects or as concepts licensed to outside buyers . Exporting ideas also gives companies a way to measure an innovation's real value . However, the authors warn against entering into open-market innovation without properly structuring deals: Xerox and TRW virtually gave away their innovations and had to stand by while other companies capitalized on them.

Ann N Y Acad Sci, 2002 Oct, 969, 245 - 50
Emergency response planning for anthrax outbreaks in bison herds of northern Canada: a balance between policy and science; Nishi JS et al.; Anthrax outbreaks in northern Canada have implications for ongoing recovery efforts for the threatened wood bison and may pose a health risk to humans, other wildlife, and domestic livestock . RWED and WBNP maintain Anthrax Emergency Response Plans (AERPs) for their respective jurisdictions . An AERP is a pre-planned logistical framework for responding effectively and rapidly to an outbreak so as to minimize spread of the disease, reduce environmental load of spores available for future outbreaks, and minimize risk to public health . In this paper, we describe the main components of an AERP and outline areas for future research.

Br J Anaesth, 2002 Aug, 89(2), 306 - 24
Chemical and biological weapons . Implications for anaesthesia and intensive care; White SM; In the wake of recent atrocities there has been renewed apprehension regarding the possibility of chemical and biological weapon (CBW) deployment by terrorists . Despite various international agreements that proscribe their use, certain states continue to develop chemical and biological weapons of mass destruction . Of greater concern, recent historical examples support the prospect that state-independent organizations have the capability to produce such weapons . Indeed, the deliberate deployment of anthrax has claimed several lives in the USA since September 11, 2001 . In the event of a significant CBW attack, medical services would be stretched . However, victim survival may be improved by the prompt, coordinated response of military and civil authorities, in conjunction with appropriate medical care . In comparison with most other specialties, anaesthetists have the professional academic background in physiology and pharmacology to be able to understand the nature of the injuries caused by CBWs . Anaesthetists, therefore, play a vital role both in the initial resuscitation of casualties and in their continued treatment in an intensive care setting . This article assesses the current risk of CBW deployment by terrorists, considers factors which would affect the severity of an attack, and discusses the pathophysiology of those CBWs most likely to be used . The specific roles of the anaesthetist and intensivist in treatment are highlighted.

Biochem Biophys Res Commun, 2002 Oct 11, 297(5), 1121 - 7
Delivery of nucleic acid into mammalian cells by anthrax toxin; Gaur R et al.; Gene delivery vehicles based on receptor-mediated endocytosis offer an attractive long-term solution as they might overcome the limitations of toxicity and cargo capacity inherent to many viral gene delivery systems . The protective antigen component of anthrax toxin bind to specific receptors and deliver lethal factor or edema factor into the cytosol of mammalian cells . The N-terminal 254 amino acids of LF (LF(1-254)) binds to PA and, when fused to heterologous proteins, delivers such proteins into the cytosol . However, so far no attempt has been made to use the anthrax toxin system for the intracellular delivery of DNA . In the present study, LF(1-254) of anthrax toxin was fused to the DNA-binding domain of GAL4 protein . The fusion protein (LF(254)-GAL4DBD) showed both PA binding as well as DNA-binding activity in solution . The complex of fusion protein with plasmid DNA containing a reporter gene (luciferase or green fluorescent protein) along with PA delivered plasmid DNA into the cytosol of COS-1 cells . These results suggest that anthrax toxin components can be used as a non-viral system for the efficient delivery of DNA into the cytosol of mammalian cells.

J Fam Pract, 2002 Sep, 51(9), 745 - 50
On the front lines: family physicians' preparedness for bioterrorism; Chen FM et al.; OBJECTIVE: The events of September 11, 2001, and the nation's recent experience with anthrax assaults made bioterrorism preparedness a national priority . Because primary care physicians are among the sentinel responders to bioterrorist attacks, we sought to determine family physicians' beliefs about their preparedness for such an attack . STUDY DESIGN: In October 2001 we conducted a national survey of 976 family physicians randomly selected from the American Academy of Family Physicians' active membership directory . POPULATION: 614 (63%) family physicians responded to the survey . OUTCOMES MEASURED: Physicians' self-reported ability to "know what to do as a doctor in the event of a suspected bioterrorist attack, recognize signs and symptoms of an illness due to bioterrorism, and know where to call to report a suspected bioterrorist attack." RESULTS: Ninety-five percent of physicians agreed that a bioterrorist attack is a real threat within the United States . However, only 27% of family physicians believed that the US health care system could respond effectively to a bioterrorist attack; fewer (17%) thought that their local medical communities could respond effectively . Twenty-six percent of physicians reported that they would know what to do as a doctor in the event of a bioterrorist attack . Only 18% had previous training in bioterrorism preparedness . In a multivariate analysis, physicians reported that preparedness for a bioterrorist attack was significantly associated with previous bioterrorism preparedness training (OR 3.9 {95% CI 2.4-6.3}) and knowing how to obtain information in the event of a bioterrorist attack (OR 6.4 {95% CI 3.9-10.6}) . CONCLUSIONS: Only one quarter of family physicians felt prepared to respond to a bioterrorist event . However, training in bioterrorism preparedness was significantly associated with physicians' perceived ability to respond effectively to an attack . Primary care physicians need more training in bioterrorism preparedness and easy access to public health and medical information in the event of a bioterrorist attack.

Vet Hum Toxicol, 2002 Oct, 44(5), 291 - 2
Believe it or not--silver still poisons!
Hori K, Martin TG, Rainey P, Robertson WO.
For centuries, silver has been endowed with therapeutic benefits . It is still used today as a "caustic" for superficial bleeding . Within 7days, we had 3 cases of "argyria" and then 2 more over the next month . The first 2 cases involved a husband and wife with a 3-y exposure to naturopathic hydrolyzed silver treatment . The third casewas a 37-y-old male in a state psychiatric facility noted to have darkly "discolored" skin probable obtained from herbal tea . The last 2 cases were a married couple into herbal medications who developed bluish discoloration of face and hands . Current cases due to "alternative medicine" may get worse as rumor reveals its popularity as prophylaxis against anthrax . The skin's grayish discoloration, made worse by sunlight, may persist for life.

Nat Rev Mol Cell Biol, 2002 Oct, 3(10), 753 - 66
Furin at the cutting edge: from protein traffic to embryogenesis and disease; Thomas G; Furin catalyses a simple biochemical reaction--the proteolytic maturation of proprotein substrates in the secretory pathway . But the simplicity of this reaction belies furin's broad and important roles in homeostasis, as well as in diseases ranging from Alzheimer's disease and cancer to anthrax and Ebola fever . This review summarizes various features of furin--its structural and enzymatic properties, intracellular localization, trafficking, substrates, and roles in vivo.

Psychol Rep, 2002 Aug, 91(1), 187 - 91
Comments on the Institute of Medicine's 2002 report on the safety of anthrax vaccine; Schumm WR et al.; In April 2002, the prestigious Institute of Medicine of the National Academy of Sciences issued a final report on the safety and effectiveness of the anthrax vaccine currently in use by the United States military . It concluded that the present vaccine was completely safe and effective, but ignored evidence of several recent research studies from three different nations that have implicated vaccines, often including anthrax vaccine, in the epidemiology of Gulf War illnesses . Omissions and limitations of that report are discussed.

Med Parazitol (Mosk), 2002 Jul-Sep, (3), 13 - 6
{Infection and invasion of humans in the Yamal Peninsula}; Fattakhov RG et al.; The helminthic fauna of vertebrates in the Yamal peninsula consists of 61 species: of them 2 species are monogenic, 6 are trematodes, 29 are cestodes, and 24 are nematodes . Twelve species of the 4 are antroponoses and 8 are zoonoses which may parasite on human beings . Human infection with some zoonoses is due to local habits of eating raw or undercooked meat of wild animals, domestic deers, and fish . These helminthic diseases include trichinosis, taeniasis, opisthorchiasis, diphyllobothriasis . On contacting with dogs and Arctic foxes, the population is infected with echinococciasis, alveococciasis, toxoplasmosis . The foci of brucellosis, anthrax, tularemia, leptospirosis, rickettsioses, rabies, and toxoplasmosis were notified in the Yamal peninsula . Intensive migration of the population contributes to the importation of new species of causative agents to the peninsula and to the deterioration of the situation of endemic invasions and infections . Thus, in-depth study of parasitic and natural focus-related diseases in this region becomes partially urgent now.

J Am Pharm Assoc (Wash), 2002 Sep-Oct, 42(5 Suppl 1), S50 - 1
Disaster planning and emergency preparedness: lessons learned; Babb J et al.; Following the terrorist attacks of September 11, 2001, the federal response plan was activated immediately, with most efforts focused on helping recovery workers at Ground Zero in New York City . Comprehensive pharmacy services were critical in protecting the health of those potentially exposed to anthrax at U.S . Postal Service facilities and the U.S . Capitol . Responding to anthrax attacks taught many valuable lessons to emergency workers on how to manage a bioterrorist attack . Because of its central place in the life of many American communities, pharmacy is a natural and important ally of public health.

Biochem Biophys Res Commun, 2002 Sep 27, 297(3), 506 - 9
Delayed treatment with doxycycline has limited effect on anthrax infection in BLK57/B6 mice; Kalns J et al.; Blk57/B6 mice were infected with LD90 dose of Sterne strain anthrax spores subcutaneously and then treated with doxycycline . Doxycycline at a dose of 1.5mg/kg, by intra-peritoneal injection, protected mice from death when given at the same time as spores . When doxycycline administration was delayed 4h survival is 90% . Delay of 24h increased survival time but had no impact on eventual mortality . When doxycycline was delayed 48h, mortality and time to death were comparable to sham injection . Peritoneal macrophages harvested from Blk57/B6 mice were examined for response to anthrax lethal toxin and are shown to be deficient in their ability to produce TNF-alpha and have increased expression of IL-6 compared to RAW 264.7 murine macrophage cell line . These findings suggest that antibiotic therapy has limited effects following lethal anthrax spore challenge, even when the host is of a phenotype that does not produce TNF-alpha in response to anthrax lethal toxin exposure.

Scand J Infect Dis, 2002, 34(8), 627 - 8
A case of anthrax meningitis; Albayrak F et al.; Meningeal anthrax is a very rare complication of the cutaneous, respiratory and gastrointestinal form of anthrax infection . Anthrax bacilli, most commonly enter the body via the skin, and the organism then disseminates to the central nervous system via the hematogenous or lymphatic routes leading to fatal bacterial meningitis, even with intensive antibacterial therapy.

Clin Infect Dis, 2002 Oct 1, 35(7), 851 - 8 Epub 2002 Aug 30.
Management of anthrax; Bartlett JG et al.; From 3 October 2001 through 16 November 2001, in the United States, there were 18 confirmed cases of inhalational and cutaneous anthrax, an additional 4 suspected cases of cutaneous anthrax, and 5 deaths due to inhalational anthrax . Although the number of cases was relatively small, this experience brought bioterrorism and its potential to sharp focus as thousands of people began receiving prophylactic antibiotics after possible exposure to anthrax spores . These events have resulted in a substantial impact on the health care system, including the rewriting of pneumonia guidelines, new emphasis on identification of microbial etiology, substantial infusion of funds for bioterrorism-related research, and a sudden mandate for regional disaster and public health planning . This article provides clinicians with clinically relevant information about the diagnosis and management of anthrax.

Risk Anal, 2002 Aug, 22(4), 655 - 64
Risk analysis and risk management in an uncertain world; Kunreuther H; The tragic attacks of September 11 and the bioterrorist threats with respect to anthrax that followed have raised a set of issues regarding how we deal with events where there is considerable ambiguity and uncertainty about the likelihood of their occurrence and their potential consequences . This paper discusses how one can link the tools of risk assessment and our knowledge of risk perception to develop risk management options for dealing with extreme events . In particular, it suggests ways that the members of the Society for Risk Analysis can apply their expertise and talent to the risks associated with terrorism and discusses the changing roles of the public and private sectors in dealing with extreme events.

Curr Top Microbiol Immunol, 2002, 271, 61 - 85
Structure and function of anthrax toxin; Lacy DB et al.; Anthrax toxin is a binary A-B toxin comprised of protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF) . In the presence of a host cell-surface receptor, PA can mediate the delivery of EF and LF from the extracellular milieu into the host cell cytosol to effect toxicity . In this delivery, PA undergoes multiple structural changes--from a monomer to a heptameric prepore to a membrane-spanning heptameric pore . The catalytic factors also undergo dramatic structural changes as they unfold to allow for their translocation across the endosomal membrane and refold to preserve their catalytic activity within the cytosol . In addition to these gross structural changes, the intoxication mechanism depends on the ability of PA to form specific interactions with the host cell receptor, EF, and LF . This chapter presents a review of experiments probing these structural interactions and rearrangements in the hopes of gaining a molecular understanding of toxin action.

Curr Top Microbiol Immunol, 2002, 271, 1 - 19
Introduction: anthrax history, disease and ecology; Turnbull PC; The familiarity with the ancient disease anthrax from the second millennium B.C . through the second millennium A.D . is reviewed, providing the backdrop to the modern understanding of this disease as covered in the remainder of the volume . By means of an overview of the aetiology, ecology, epidemiology, clinical manifestations, pathology and bacteriology of the naturally acquired disease, this opening chapter also lays down the groundwork for the subsequent state-of-the-art chapters.

Med Sci Monit, 2002 Sep, 8(9), CS73 - 6
GI anthrax: report of one case confirmed with autopsy; Mansour-Ghanaei F et al.; BACKGROUND: Bacillus Anthraces is a non-motile, rod like, gram-positive and aerobic bacillus that produces central oval-shaped spores and characterized by rough, irregular and often comma-shaped colonies in blood agar . About 95% of human anthrax is cutaneous and 5% respiratory . GI anthrax, a very rare type, has been reported in less than 1% of all cases . We thus report a case of GI anthrax with autopsy findings . CASE REPORT: A 15-year-old young adult man was admitted to our hospital with history of fever, abdominal pain and bloody diarrhea from 48 hours after ingestion of half-cooked sheep's meat . In endoscopic exam of upper GI tract, the esophagus had been filled with fresh blood without any varices, stomach showed evidence of hemorrhage and had multiple erosion but no ulceration of duodenum . Penicillin G 24,000,000 U/day IV was started but unfortunately severe upper and lower GI hemorrhage developed, leading to hypotension and death . In autopsy, ascites, paraaortic and mesenteric lymphadenopathy was accident with some of them being hemorrhagic . The spleen was slightly enlarged with hemorrhagic congestion in some parts of it . In the blood sample drawn from the spleen, the filamentous bacillus was successfully found . CONCLUSIONS: Because of the fatal nature of the disease and the similarity of the signs and symptoms to the other gastrointestinal diseases, we should consider it as one of the probable differential diagnosis in the patients with upper and lower gastrointestinal bleeding with fever esp . in the endemic areas.

Med Confl Surviv, 2002 Jul-Sep, 18(3), 271 - 82
A short history of biological warfare; Metcalfe N; Biological weapons have been used in war from the start of recorded history . This article reviews the history of the subject, including the outbreak of the Black Death and the use of smallpox against American Indians . The new science of microbiology was misused from soon after its start and, despite the 1925 Geneva Protocol, the Japanese experimented extensively on prisoners in China . The Allies carried out extensive research during the Second World War, notably the United Kingdom into anthrax on Gruinard Island and the United States into a variety of agents . Despite the 1972 Biological Weapons Convention (BWC), a major programme continued in the former Soviet Union (leading to an accidental outbreak of anthrax) . Most recently Iraq was revealed as having an extensive programme, with weaponization of large amounts of various agents, and several terrorists groups have attempted to use biological agents as weapons . Modern developments in biotechnology could lead to even more serious developments, and effective preventive measures, including strengthening of the BWC, are imperative.

J Trop Pediatr, 2002 Aug, 48(4), 225 - 6
Cutaneous anthrax: an endemic outbreak in south India; Vijaikumar M et al.; Although human anthrax has become rare, endemic outbreaks still occur in tropical countries, parts of South America and Europe . We report 23 cases of cutaneous anthrax due to an endemic outbreak of animal and human anthrax in South India . These patients were admitted to our hospital between July 1998 and July 2001 . Children outnumbered adults and most of them had lesions on the exposed sites . The majority of patients reported the death of infected animals in the neighbourhood without any direct contact with dead animals . Hence, vector borne transmission was suspected in most of the cases . Diagnosis was confirmed by the presence of a typical ulcer with eschar, Gram-stained smears from ulcers and epidemiological evidence . Except for one fatal case, all patients responded to treatment.

Clin Microbiol Infect, 2002 Aug, 8(8), 510 - 21
A procedure for differentiating between the intentional release of biological warfare agents and natural outbreaks of disease: its use in analyzing the tularemia outbreak in Kosovo in 1999 and 2000; Grunow R et al.; The events of 11 September and the subsequent anthrax outbreaks in the USA have opened the world's eyes to the threat posed by terrorist groups, criminal organizations and lone operators who will stop at nothing to achieve their goals . The open or covert use of pathogens and toxins as biological warfare agents can no longer be ruled out . Against this background, the appearance of an unusual disease must be studied in order to clarify whether it is a natural or artificially caused occurrence . This issue was recently raised in discussions with local representatives and relief organizations during a tularemia epidemic in Kosovo from October 1999 to May 2000 . This paper will present a procedure which attempts to use certain criteria to identify or rule out the use of biological warfare agents in the event of an unusual outbreak of disease . Data and findings gathered by routine epidemiologic and microbiological studies often provide only an indirect answer to this problem . For this reason, various criteria were formulated and points allocated to represent their importance, allowing us to deduce in a semiquantitative manner the degree of possibility of an artificial genesis of outbreaks . The significance and characterization of each criterion are discussed . An analysis of the tularemia epidemic in Kosovo based on the procedure described here indicates that a deliberate release of the causative agent of tularemia, Francisella tularensis, as a biological warfare agent is doubtful . In this paper, an approach is described to discriminate between the intentional use of biological warfare agents and natural outbreaks of infectious diseases . The developed model is flexible and considers the political, military and social analysis of the crisis-afflicted region, the specific features of the pathogen, and the epidemiologic and clinical characteristics of the epidemic.

Clin Microbiol Infect, 2002 Aug, 8(8), 489 - 503
Anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room; Cunha BA; Bioterrorism has become a potential diagnostic consideration in infectious diseases . This article reviews the clinical presentation and differential diagnosis of potential bioterrorist agents when first presenting to the hospital in the emergency room setting . The characteristic clinical features of inhalation anthrax, tularemic pneumonia, plague pneumonia, including laboratory and radiographic finding, are discussed . Ebola vieus and smallpox are also discussed as potential bioterrorist-transmitted infections from the clinical and epidemiologic standpoint . In addition to the clinical features of the infectious diseases mentioned, the article discusses the infectious disease control and epidemiologic implications of these agents when employed as bioterrorist agents . The review concludes with suggestions for postexposure prophylaxis and therapy.

Vaccine, 2002 May 31, 20 Suppl 3, S48 - 50
Aluminum-containing vaccine associated adverse events: role of route of administration and gender; Pittman PR; Anthrax vaccine, adsorbed (AVA) is a vaccine containing aluminum hydroxide that is administered as six subcutaneous (s.q.) doses over 18 months . It is the only aluminum hydroxide licensed for s.q . administration . To optimize the vaccination schedule and route of administration, a prospective pilot study comparing the use of fewer doses administered intramuscularly (i.m.) as well as s.q . with the licensed schedule and route was performed . Data from that study on injection site reactions were extracted for this report . Erythema and induration occurred more commonly when the vaccine was administered s.q . compared to i.m . (P < 0.0001, P = 0.002, respectively) . S.q . nodules were found only among the s.q . group (P < 0.0001) . Erythema, induration and s.q . nodules were more common in women compared with men (P < 0.001) after the first s.q . dose of AVA dose . Reaction rates decreased when the interval between the first two doses of AVA was increased from 2 to 4 weeks.

Infect Immun, 2002 Sep, 70(9), 4997 - 5007
Anthrax edema toxin requires influx of calcium for inducing cyclic AMP toxicity in target cells; Kumar P et al.; The anthrax edema toxin comprises two proteins: protective antigen and edema factor . Anthrax protective antigen binds to the receptors on the surface of target cells and facilitates the entry of edema factor into these target cells . Edema factor (EF) is an adenylate cyclase that catalyzes the synthesis of cyclic AMP (cAMP) in the cytosol of the host cells . In this study, we examined the requirement of extracellular calcium for anthrax edema toxin-induced toxicity in host cells . The cAMP response generated by edema toxin was analyzed in a variety of cells, including CHO, macrophage-like RAW264.7, human neutrophils, and human lymphocytes . Our investigations reveal that after EF reaches the cell cytosol, a rapid influx of calcium is triggered in the host cell that has a pivotal role in determining the cAMP response of the affected cells . Although the cAMP response generated by edema toxin in different cell types varied in intensity and in the time of initiation, the influx of calcium invariably preceded cAMP accumulation . Agents that blocked the uptake of calcium also inhibited edema toxin-induced accumulation of cAMP in the host cells . This is the first report that demonstrates that edema toxin induces accumulation of cAMP in lymphocytes . By accumulating cAMP, a potent inhibitor of immune cell function, edema toxin may actually be poisoning the immune system and thus facilitating the survival of the bacteria in the host.

Neurology, 2002 Aug 13, 59(3), 327 - 34
Anthrax meningoencephalitis; Lanska DJ; 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.

Chest, 2002 Aug, 122(2), 741 - 5
Hypersensitivity pneumonitis following anthrax vaccination; Timmer SJ et al.; A case of hypersensitivity pneumonitis (HP) following anthrax vaccination is described . The patient is a 39-year-old, previously healthy man on active duty in the US Marine Corps, in whom a urticaral skin rash and progressive dyspnea on exertion developed following subcutaneous anthrax vaccination . A diagnosis of bronchiolitis obliterans with organizing pneumonia was made from transbronchial lung biopsy samples after evaluation excluded multiple infectious and collagen vascular etiologies . This appears to be the first recorded case of HP following an anthrax vaccination; however, a case report of pulmonary and cutaneous vasculitis following hepatitis B vaccination has been reported in the literature and is reviewed.

Harefuah, 2002 May, 141 Spec No, 4 - 6, 124
{Characteristics of anthrax: its description and biblical name--Shehin}; Ben-Noun L; The illness known as Anthrax is very rare in the west . In developing countries relatively significant numbers of cases are found, particularly in animals . However, biological terrorist acts could cause it to spread . In Hebrew, the illness is now called Gahelet or Gameret . The purpose of this paper is to examine whether the illness is described in the Bible, and if so, to present that description and provide a broader survey of the features of this illness . The word Gahelet appears in the Bible, but not indicating a disease, while the source of Gameret is in the Talmud . In the Bible, Shehin is mentioned as the sixth of the ten plagues in Egypt, and also as the disease that affected Job . The natural course of the condition, as described in the Bible, matches the clinical symptoms of Anthrax, as we know it today . The Hebrew Language Academy is therefore advised to adopt the findings of this paper, and confirm the name of the illness in Israel--Shehin.

Harefuah . 2002 May;141 Spec No:21, 123.
{National preparedness for biological mass casualty event: between the devil and the deep blue sea}; Eldad A; Species of plants and animals, as well as nations of human beings were extinguished throughout the prehistory and history of this planet . One of the possible explanations for this phenomenon is a large scale epidemic of viral, bacterial or fungal infections . One well-documented example was the smallpox epidemic among native Indians of South America following the European invasion . Deliberate dissemination of disease was used as a weapon during the Middle Ages when corpses of plague casualties were thrown over the walls and into the besieged towns . The Book of Kings II, of the Bible, in chapter 19 recalls the story of 185,000 soldiers of Sennacherib that died in one night, near the walls of Jerusalem . The possibility of causing mass casualty by dissemination of infectious disease has driven countries and terrorist organizations to produce and store large quantities of bacteria or viruses . The death of thousands in the USA on September 11, 2001, demonstrated that terror has no moral prohibitions, only technical limitations . Terror organizations will not hesitate to use weapons for mass destruction to kill many, and if only few will die, it will still serve the purpose of these evil organizations: to strew panic, to destroy normal life and to increase fear and instability . Any government that faces decisions about how to be better prepared against biological warfare is pushed between the devil and the deep blue sea . On the one hand: the better we will be prepared, equipped with antibiotics and vaccines--the more lives of casualties we will be able to save . Better public education will help to reduce the damage, but, on the other hand--in order to cause more people to make the effort to equip themselves or to refresh their protective kit--we will have to increase their level of concern . In order to improve the medical education of all members of the medical teams we will have to start a broad and intense campaign, thereby taking the risk of increasing stress in the public in anticipation of such an attack . The more we will encourage patients who suffer flu-like syndromes to consult their family physician, the more instances of early detection of anthrax cases we will discover . However, in so doing, we will increase the level of national stress and flood primary medicine with many thousands of patients without being able to give our general practitioners any simple and effective tool for the diagnosis of anthrax in its early stages . Between the devil of biological warfare and the deep blue sea of public reaction, a small group of decision-makers and their professional advisers is under pressure . Israel is fortunate that this is not a new problem for this group of experts . Large scale drills, thorough preparations and adequate stockpiling of everything required marks the results of this group's activities . The state of Israel is today one of the best-prepared countries for such an event.

Harefuah, 2002 May, 141 Spec No, 13 - 5, 124
{Bioterrorism}; Oren M; The terror attacks of the September 11, 2001 in the U.S.A followed by the proliferation of anthrax using mail in some US cities and abroad, demonstrated the complex, devastating and harmful nature of terror activity . The use of weapons of mass destruction (WMD) in terrorist activities is a reality as is the use of biological weapons (BW) in bioterrorism . Cyberterrorism is another form of non-conventional terrorism . The health care system throughout all its different components and layers--public health, primary care, hospitals, first responders etc., must be prepared . The complete network must have a comprehensive contingency plan for any possible BW scenario . The health care system must cope successfully with the challenge of early diagnosis of extraordinary illness or outbreak of disease, having the ability to define any bioterror event and to conduct appropriate risk assessments . It is of great importance to prepare in advance a comprehensive coordinated plan with all other governmental ministries and agencies . In order to succeed it is crucial that the top decision makers--the Prime Minister and government members and top ranking officials at the Ministry of Health, be committed, and continuously proactive in the complicated and lengthy process of preparing the health care system for a bioterrorism event.

Harefuah, 2002 May, 141 Spec No, 100 - 4, 119, 118
{Tetracyclines and ciprofloxacin as treatment for children and pregnant or lactating women in the era of biological terror}; Aizenstien O et al.; Many forms of bacteria, such as anthrax, can be used as biological weapons . According to the CDC guidelines, Ciprofloxacin or Doxycycline is recommended for antimicrobial prophylaxis against anthrax for 60 days . Since October 8, approximately 32,000 persons with potential exposure to anthrax have initiated antimicrobial prophylaxis, mainly with Ciprofloxacin . Children and pregnant and lactating women are likely to be among the increasing number of persons receiving Ciprofloxacin or Doxycycline as a prophylaxis regardless of the potential danger of these drugs . Once the bacteria in question are shown to be sensitive to other antibiotics, treatment should be switched to antibiotics that are commonly used in children and pregnant women . The main consideration in prescribing these antibiotics is the fear of anthrax morbidity and mortality, as opposed to the risk of antibiotic side effects . The best treatment should be provided even though it can cause side effects . This paper reviews the information about the indications, dosage and side effects of Ciprofloxacin and Doxycycline in children and pregnant women and lactating women.

Biomedica, 2002 Jun, 22(2), 106 - 9
{Species of the Bacillus strain: macroscopic and microscopic morphology}; Realpe ME et al.; Between October 2001 and January 2002, the Microbiology Group of the Instituto Nacional de Salud processed 705 envelopes under suspicion of harboring anthrax spores . We present photographs of cultures and slides prepared from them of Bacillus species to be used as reference material for the accurate macroscopic and microscopic identification of the agent found in samples.

AACN Clin Issues, 2002 Aug, 13(3), 452 - 69
Issues in preparedness for biologic terrorism: a perspective for critical care nursing; O'Connell KP et al.; Although the use of microorganisms as weapons is as old a practice as war itself, the sense of our collective vulnerability to these agents has seldom been as great . The events of late 2001 demonstrated that the United States is vulnerable to terrorist attack carried out by highly motivated, organized, funded, and trained individuals . It is our collective good fortune that the perpetrator of the anthrax mailings was not bent on destruction of the scale witnessed on September 11, 2001 . Because acute care and critical care nurses are on the forefront of community disease surveillance, they must be aware of the signs and symptoms of illness that may indicate that a biological attack has taken place . Many symptoms of infection or intoxication by biological warfare agents (bacterial, viral, and toxic) are nonspecific and flulike in nature, at least early in the disease process . The essential details of the presentation, diagnosis, treatment, and prophylaxis of the biological warfare agents that merit greatest concern are provided, and five biological warfare agents of particular interest are described in detail: anthrax, ricin (castor bean) toxin, smallpox, plague, and tularemia . Recommendations are given for additional Web-based resources to allow further study.

Acta Medica (Hradec Kralove), 2002, 45(1), 3 - 5
Anthrax toxin characterization; Patocka J et al.; The anthrax toxin comprises three proteins . When they work together, they can kill humans, especially after spores of the bacteria have been inhaled . One anthrax protein, called protective antigen (PA), chaperones the two other toxins into human or animal cells and shields them from the body's immune system . The second, lethal factor (LF), destroys the white blood cells that hosts send in defence . The third toxin molecule, edema factor (EF), hijacks the signaling system in the body . This disrupts the energy balance of cells and leads to them accumulating fluid and complete destroy of cells.

Protein Pept Lett, 2002 Feb, 9(1), 1 - 14
Peptide toxins directed at the matrix dissolution systems of cancer cells; Frankel AE et al.; Growth and spread of tumors requires a variety of membrane and extracellular proteases to modify membrane integrins, dissolve the surrounding matrix and release critical growth factors from both the tumor cell surface and surrounding structures . The two major protease systems involved in this process are the matrix metalloproteases and the serine proteases . Genes and gene products for both protease systems are overexpressed in a variety of neoplasms . Thus, these enzymes serve as excellent targets for the delivery of potent cytotoxic molecules to tumors . A number of peptide toxins have been engineered to bind to tumor cells with high levels of surface proteases and their receptors including anthrax toxins, Pseudomonas exotoxin, saporin and diphtheria toxin . These recombinant fusion proteins provide a novel class of anti-cancer agents that will enter clinical trials in the next several years.

Zh Mikrobiol Epidemiol Immunobiol, 2002 May-Jun, (3), 3 - 12
{Problem of bioterrorism under modern conditions}; Vorob'ev AA et al.; It is practically impossible to discuss the problem of bioterrorism (BT) and to develop effective programs of decreasing the losses and expenses suffered by the society from the BT acts without evaluation of the threat and prognosis of consequences based on research and empiric data . Stained international situation following the act of terrorism (attack on the USA) on September 11, 2001, makes the scenarios of the bacterial weapon use (the causative agents of plague, smallpox, anthrax, etc.) by international terrorists most probable . In this connection studies on the analysis and prognostication of the consequences of BT, including mathematical and computer modelling, are necessary . The authors present the results of initiative studies on the analysis and prognostication of the consequences of the hypothetical act of BT with the use of the smallpox causative agent in a city with the population of about 1,000,000 inhabitants . The analytical prognostic studies on the operative analysis and prognostication of the consequences of the BT act with the use of the smallpox causative agent has demonstrated that the mathematical (computer) model of the epidemic outbreak of smallpox is an effective instrument of calculation studies . Prognostic evaluations of the consequences of the act of BT under the conditions of different reaction of public health services (time of detection, interventions) have been obtained with the use of modelling . In addition, the computer model is necessary for training health specialists to react adequately to the acts of BT with the use of different kinds of bacteriological weapons.

Exp Mol Pathol, 2002 Aug, 73(1), 19 - 27
Antibodies to squalene in recipients of anthrax vaccine; Asa PB et al.; We previously reported that antibodies to squalene, an experimental vaccine adjuvant, are present in persons with symptoms consistent with Gulf War Syndrome (GWS) (P . B . Asa et al., Exp . Mol . Pathol 68, 196-197, 2000) . The United States Department of Defense initiated the Anthrax Vaccine Immunization Program (AVIP) in 1997 to immunize 2.4 million military personnel . Because adverse reactions in vaccinated personnel were similar to symptoms of GWS, we tested AVIP participants for anti-squalene antibodies (ASA) . In a pilot study, 6 of 6 vaccine recipients with GWS-like symptoms were positive for ASA . In a larger blinded study, only 32% (8/25) of AVIP personnel compared to 15.7% (3/19) of controls were positive (P > 0.05) . Further analysis revealed that ASA were associated with specific lots of vaccine . The incidence of ASA in personnel in the blinded study receiving these lots was 47% (8/17) compared to an incidence of 0% (0/8; P < 0.025) of the AVIP participants receiving other lots of vaccine . Analysis of additional personnel revealed that in all but one case (19/20; 95%), ASA were restricted to personnel immunized with lots of vaccine known to contain squalene . Except for one symptomatic individual, positive clinical findings in 17 ASA-negative personnel were restricted to 4 individuals receiving vaccine from lots containing squalene . ASA were not present prior to vaccination in preimmunization sera available from 4 AVIP personnel . Three of these individuals became ASA positive after vaccination . These results suggest that the production of ASA in GWS patients is linked to the presence of squalene in certain lots of anthrax vaccine.

J Assoc Physicians India, 2002 Jul, 50, 913 - 5
Problem of timely diagnosis in anthrax meningitis; Kanungo R et al.; Anthrax continues to remain a problem in parts of India . Meningitis is often a complication encountered among cases with cutaneous anthrax . We have encountered a dozen cases of anthrax meningitis in our hosptal in the past decade . A sudden unexplained rise in cases in the past two years with hundred percent mortality stresses the need for rapid confirmatory diagnosis . Most of the cases admitted with central nervous system involvement had a provisional diagnosis of conditions other than anthrax meningitis . A strong clinical suspicion with a simple Gram stain smear of the CSF will help confirm anthrax meningitis in endemic areas.

Emerg Med Clin North Am, 2002 May, 20(2), 477 - 500
Bioterrorism preparedness . III: State and federal programs and response; Mothershead JL et al.; Management of a bioterrorism event will begin with early detection and intervention at the local level . Any large-scale event will require rapid state and federal assistance . Federal initiatives targeting bioterrorism have increasingly become a complex web of executive and legislative actions, frequently initiated in reaction to specific events, and often unrelated to this threat . Multiple executive and legislative branch actions have resulted in a proliferation of federal programs, and coordination of these efforts remains a significant challenge . Still, great strides have been taken to improve our defensive posture against this emerging threat, and, at all levels, governmental authorities and agencies are much better prepared to respond to such events than they were a decade ago . The events of September 11, 2001 and subsequent events are clear indicators that the timeline for preparedness has been significantly compressed . Federal emergency operations, historically designed more for recovery than response, seemed up to the task in the wake of the World Trade Center and Pentagon attacks, although there was criticism of federal responsiveness to the subsequent anthrax incidents {71,72}, and the timeliness of federal resources in the event of a large-scale outbreak resulting from a bioterrorism attack has yet to be truly tested . The recent establishment of the Office of Homeland Security and the Homeland Security Council holds promise that some of these inefficiencies may be rectified and overall coordination of programs will improve . Continued improvements in the effectiveness of the federal government in meeting the challenges of this and other emerging threats to homeland security will require: Establishment of consensus standards, metrics, and measures of effectiveness for all aspects of disaster, epidemic, and terrorism management at the local, regional, state, and federal levels Delineation of expected, quantifiable state and local capabilities to mitigate, prepare, respond, and recover from all disasters, including those caused by terrorist actions Development of predefined or clear and rapidly discernible criteria for deployment of state and federal emergency resources Full accountability of program costs and expenditures Continued consolidation or coordination of the many overlapping and at times redundant federal programs.

Emerg Med Clin North Am, 2002 May, 20(2), 351 - 64
Medical management of the suspected victim of bioterrorism: an algorithmic approach to the undifferentiated patient; Henretig FM et al.; We have purposely expanded on the well-known ATLS paradigm to aid EHCPs in their approach to a potential bioterrorism event . By building on a process that is already familiar, we hope this will aid the EHCP to remember a systematic approach to such an incident . By following this ten-step process, we believe that all EHCPs, and especially those practicing at the first echelons of care in urgent care clinics and EDs, can approach the daunting problem of biological defense with a good deal more confidence . This same model advocated for bioterrorism also may apply to natural infectious disease epidemics, particularly of emerging or re-emerging diseases, that might not be optimally managed by reliance on the conventional public health strategy that requires physician-dependent definitive diagnosis and active reporting mechanisms . The authors hope the acquired knowledge and skills one might gain will rarely be needed, but if the events surrounding the dispersal of anthrax-contaminated mail in the fall of 2001 are any indication of the future, such competencies will be invaluable.

Emerg Med Clin North Am, 2002 May, 20(2), 273 - 309
Threats in bioterrorism . I: CDC category A agents; Darling RG et al.; Although once considered unlikely, bioterrorism is now a reality in the United States since the anthrax cases began appearing in the fall of 2001 . Intelligence sources indicate there are many countries and terrorist organizations that either possess biological weapons or are attempting to procure them . In the future it is likely that we will experience additional acts of bioterrorism . The CDC category A agents represent our greatest challenge because they have the potential to cause grave harm to the medical and public health systems of a given population . Thus, it is imperative that plans be developed now to deal with the consequences of an intentional release of any one or more of these pathogens.

Isr Med Assoc J, 2002 Jul, 4(7), 498 - 502
The epidemiologic pyramid of bioterrorism; Huerta M et al.; Recent events have drawn world attention to "mythological diseases"--such as anthrax, plague and smallpox--which have been out of the spotlight for some decades . Much of our current knowledge of epidemic intervention and disease prevention was acquired over history through our experience with these diseases, such that the sudden panic over the reemergence of these historically well-known entities is perplexing . Over time, changes in the balance of the epidemiologic triangle have driven each of these disease systems towards a new equilibrium with which we are not familiar . While the pathogens may be similar, these are not the diseases of the past . These new disease systems are insufficiently described by the classic epidemiologic triangle, which lacks a dimension necessary for providing a valid model of the real-world effects of bioterror-related disease . Interactions within the classic epidemiologic triangle are now refracted through the prism of the global environment, where they are mediated, altered, and often amplified . Bioterror-associated diseases must be analyzed through the epidemiologic pyramid . The added dimension represents the global environment, which plays an integral part in the effects of the overall disease system . The classic triangle still exists, and continues to function at the base of the new model to describe actual agent transmission, but the overall disease picture should be viewed from the height of the fourth apex of the pyramid . The epidemiologic pyramid also serves as a practical model for guiding effective interventional measures.

Isr Med Assoc J, 2002 Jul, 4(7), 495 - 7
Preparedness of the Israeli health system for a biologic warfare event; Sagi R et al.; The threat of a disease outbreak resulting from biologic warfare has been of concern for the Israeli health system for many years . In order to be prepared for such an event the health system has formulated doctrines for various biologic agents and defined the logistic elements for the procurement of drugs . During the last 4 years, and especially after the West Nile fever epidemic in 2000, efforts to prepare the healthcare system and the relevant organizations were accelerated . The Director-General of the Ministry of Health nominated a Supreme Steering Committee to fill in the gaps and upgrade the preparedness of the health system for an unusual disease outbreak . This committee and its seven subcommittees established appropriate guidelines, communication routes among different organizations, and training programs for medical personnel . The anthrax outbreak in the United States found the healthcare system in the hub of the preparation process, and all modes of action were intensified . Further work by hospitals, primary care clinics and all other institutes should be increased to maintain a state of proper preparedness.

Infect Immun, 2002 Aug, 70(8), 4477 - 84
Identification of amino acid residues of anthrax protective antigen involved in binding with lethal factor; Chauhan V et al.; Protective antigen (PA) and lethal factor (LF) are the two components of anthrax lethal toxin . PA is responsible for the translocation of LF to the cytosol . The binding of LF to cell surface receptor-bound PA is a prerequisite for the formation of lethal toxin . It has been hypothesized that hydrophobic residues P184, L187, F202, L203, P205, I207, I210, W226, and F236 of domain 1b of PA play an important role in the binding of PA to LF . These residues are normally buried in the 83-kDA version of PA, PA83, as determined by the crystal structure of PA . However, they become exposed due to the conformational change brought about by the cleavage of PA83 to PA63 by a cell surface protease . Mutation of the above-mentioned residues to alanine resulted in mutant proteins that were able to bind to the cell surface receptors and also to be specifically cleaved by the cellular proteases . All the mutant proteins except the F202A, L203A, P205A, and I207A mutants were able to bind to LF and were also toxic to macrophage cells in combination with LF . It was concluded that residues 202, 203, 205, and 207 of PA are essential for the binding of LF to PA.

Med Pr, 2002, 53(2), 167 - 72
{Anthrax as biological warfare weapon}; Zajkowska J et al.; Anthrax-disease of herbivorous animals, occasionally affecting humans, is regarded as an ideal biowarfare weapon . This was witnessed during a tragic accident in Swierdlowsk some time ago and nowadays it has been observed among post office workers in the USA . Depending on the way the pathogen enters the body, several forms of disease develops: skin anthrax specific for the man (with mortality up to 20%), intestinal anthrax resulting from the consumption of infected food or flash of infected animals (with mortality up to 60-80%) and inhalation pulmonary anthrax (with mortality up to 90%) . The lethal effects of disease are due to a toxin composed of three agents . It is recommended that the exposed persons be given antibiotics to prevent them from the development of acute forms of the disease . Bearing in mind that there are B . anthracis strains resistant to Penicillin and Doxycyclin, Ciprofloxacin should be given to the patients, including children, pregnant women (for 60 days until determining antibiotic resistance) and immuno-compromised persons . In single cases--intravenous, and in a large number of cases--oral treatment is recommended.

Ann N Y Acad Sci, 2002 Jun, 966, 327 - 42
Immunological responses are not abnormal in symptomatic Gulf War veterans; Everson MP et al.; The underlying etiology and pathogenesis of Gulf War veterans' illnesses continue to be under intense investigation . Reports have suggested the basis for these illnesses may be an altered immune system, but compelling evidence is lacking . We sought to determine whether in vitro immune responses were abnormal in symptomatic Gulf War veterans relative to matched controls . A randomized case-control study was conducted by blinded comparison of laboratory measures of in vitro immune responses in blood samples obtained from veterans in an outpatient facility of a Veterans Affairs medical center . Symptomatic Gulf War veterans with otherwise undefined illnesses (52 symptomatic subjects), asymptomatic Gulf War veterans (31 asymptomatic controls), and veterans who had applied for disability compensation and had not participated in the Gulf War (21 disability controls) represented the volunteer sample . In vitro cellular and humoral immune responses were measured to detect functional abnormalities in antigen presenting cells (autologous mixed leukocyte reactions and expression of interleukin (IL)-1beta, IL-6, IL-10, and tumor necrosis factor-alpha); T cells (lymphocyte proliferation using the polyclonal T-cell activators phytohemagglutinin and Concanavalin A; primary immune responses in allogeneic mixed leukocyte reactions; secondary immune response using the recall antigens tetanus toxoid, Candida albicans, and anthrax vaccine; and soluble IL-2 receptor expression); type-1 T-helper cells (gamma interferon expression); type-2 T-helper cells (IL-4 and IL-10 expression); and B cells (polyclonal B-cell activator pokeweed mitogen-induced immunoglobulin production) . In general, immune response measures did not differ significantly between groups . Heightened responses observed in the disability control group (sporadically greater responses to one mitogen and two antigens) and the Gulf War participation control group (greater recall responses to anthrax vaccine) did not suggest impaired immune cell function in symptomatic veterans when compared with controls . We conclude that in vitro immunological responses are not abnormal in symptomatic Gulf War veterans.

FEMS Microbiol Lett, 2002 Jul 2, 212(2), 183 - 6
Asp 187 and Phe 190 residues in lethal factor are required for the expression of anthrax lethal toxin activity; Singh A et al.; Anthrax toxin consists of three proteins, protective antigen, lethal factor, and edema factor . Protective antigen translocates lethal factor and edema factor to the cytosol of mammalian cells . The amino-termini of lethal factor and edema factor have several homologous stretches . These regions are presumably involved in binding to protective antigen . In the present study we have determined the role of one such homologous stretch in lethal factor . Residues 187AspLeuLeuPhe190 were replaced by alanine . Asp187Ala and Phe190Ala were found to be non-toxic in combination with protective antigen . Their protective antigen-binding ability was drastically reduced . We propose that Asp187 and Phe190 are crucial for the expression of anthrax lethal toxin activity.

Biologist (London) . 2002 Jun;49(3):140.
Bioterrorism today; Snell N; Anthrax being sent through the postal service brought the risks of bioterrorism home to us all: but what dies it really mean?

Emerg Infect Dis, 2002 Jul, 8(7), 649 - 51
Anthrax of the gastrointestinal tract; Sirisanthana T et al.; When swallowed, anthrax spores may cause lesions from the oral cavity to the cecum . Gastrointestinal anthrax is greatly underreported in rural disease-endemic areas of the world . The apparent paucity of this form of anthrax reflects the lack of facilities able to make the diagnosis in these areas . The spectrum of disease, ranging from subclinical infection to death, has not been fully recognized . In some community-based studies, cases of gastrointestinal anthrax outnumbered those of cutaneous anthrax . The oropharyngeal variant, in particular, is unfamiliar to most physicians . The clinical features of oropharyngeal anthrax include fever and toxemia, inflammatory lesion(s) in the oral cavity or oropharynx, enlargement of cervical lymph nodes associated with edema of the soft tissue of the cervical area, and a high case-fatality rate . Awareness of gastrointestinal anthrax in a differential diagnosis remains important in anthrax-endemic areas but now also in settings of possible bioterrorism.

J Am Vet Med Assoc, 2002 Jun 15, 220(12), 1782 - 7
Perceptions of state public health officers and state veterinarians regarding risks of bioterrorism in the United States; Tharratt RS et al.; OBJECTIVE:To assess perceptions of state public health officers and state veterinarians in the United States regarding the risks of bioterrorism and determine the degree of support provided for activities related to bioterrorism . DESIGN: Cross-sectional survey . SAMPLE POPULATION: State public health officers and state veterinarians . PROCEDURE: A questionnaire was sent between April and June 2001 to the state public health officer and state veterinarian in each of the 50 states and the District of Columbia . RESULTS: Perceptions of the risk of bioterrorism attacks were similar for state public health officers and state veterinarians . Veterinarians perceived the risks associated with foot-and-mouth disease and Newcastle disease to be higher than did physicians . State veterinarians perceived the risks associated with an anthrax hoax, brucellosis, and ricin toxicosis to be lower than did state public health officers . Risk posed by agents that affected animals exclusively was perceived to be higher than risk posed by agents that affected humans exclusively and zoonotic agents . Number of full-time-equivalent positions devoted to bioterrorism surveillance and percentage of the budget devoted to bioterrorism activities were significantly lower for offices run by state veterinarians than for offices run by state public health officers . State veterinarians were significantly less likely to have knowledge of bioterrorism incidents within their state or district than were state public health officers . CONCLUSIONS AND CLINICAL RELEVANCE: Provision of additional resources to state veterinarians and explicit integration of their expertise and surveillance capabilities may be important to effectively mitigate the risk of bioterrorism.

Risk Anal, 2002 Jun, 22(3), 405 - 13
A perspective: risk analysis as a tool for reducing the risks of terrorism; Deisler PF Jr; The destruction by terrorists of the twin towers of the World Trade Center and major damage wrought to the Pentagon on September 11, 2001, followed closely by the bioterrorist anthrax attacks via the mails raised the question of whether risk analysis might have a place in defending the United States against terrorist attacks . After first reviewing the multifaceted nature of terrorism and the reasons it is likely to become endemic in world society in the long term, just as other areas of crime are endemic, this article surveys several fields of risk analysis, finding possible short- and long-term uses of risk analysis . The areas chiefly considered are: risk communication and chemical, biological, and technological risk analysis . Broad policy and other uses are also considered . The author finds that risk analysis has already played some role, perhaps informally, but he sees the possibility for a much larger, formal one, a role that is centrally important for the present and future of the United States and the world.

Am J Health Syst Pharm, 2002 Jun 15, 59(12), 1193 - 9
2001 anthrax crisis in Washington, D.C.: pharmacists' role in screening patients and selecting prophylaxis; Montello MJ et al.; Pharmacists' development and use of a worksheet facilitating their rapid selection of patient-appropriate prophylactic antimicrobials in an anthrax clinic is described . A clinic housed at D.C . General Hospital, in Washington, D.C., treated most of the people--many of them postal workers--who may have been exposed to anthrax in that city during the 2001 anthrax crisis . A form was needed to assist pharmacists in the rapid selection of prophylactic antimicrobials and in patient education and counseling . A team of pharmacists collaborated on the development of a form tailored to the clinical and logistical needs of the operation . The questions on the form were based largely on the two antianthrax agents most likely to be used, ciprofloxacin and doxycycline, and were designed to identify the circumstances that would most frequently require a medication change or a modification of patient education . Yes-or-no check boxes allowed pertinent data to be captured most efficiently . A positive response to any question triggered a personal interview and assessment by a pharmacist . A treatment algorithm was also developed to ensure consistent pharmacist selection of agents in the face of potentially changing policies and staff . The worksheet questions sought to establish treatment objectives, document allergies and concomitant therapies, and identify patients who were pregnant or lactating . Pharmacists developed a patient-screening worksheet that helped determine their choice of treatment for people who may have been exposed to anthrax in Washington, D.C., during the 2001 anthrax crisis.

Am J Health Syst Pharm, 2002 Jun 15, 59(12), 1189 - 92
2001 anthrax crisis in Washington, D.C.: clinic for persons exposed to contaminated mail; Haffer AS et al.; 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.

Eur J Clin Microbiol Infect Dis, 2002 Apr, 21(4), 258 - 61 Epub 2002 Apr 12.
Anthrax in adults and children: a review of 132 cases in Turkey; Kaya A et al.; In this retrospective study, 132 cases of anthrax observed in a Turkish hospital over a 14-year period (October 1986 to October 2000) were evaluated with respect to clinical features, therapy, and outcome . The results show that anthrax is a disease of significance in the Eastern Anatolian region of Turkey . Preventive measures such as education of the population and vaccination of animals against anthrax would reduce the incidence of the disease.

Med J Aust, 2002 Jun 17, 176(12), 605 - 8
Biological agents as weapons 2: anthrax and plague; Whitby M et al.; Although most naturally occurring infections with anthrax and plague are cutaneous, both organisms are most likely to be deliberately disseminated in aerosolised form, resulting in severe pulmonary illness . Mortality from both would be high and rapid in the absence of early and effective treatment, making swift and effective liaison between alert clinicians and public health authorities crucial to an effective response . Differentiating features include mediastinal widening (anthrax) and haemoptysis (plague) . Doxycycline and ciprofloxacin are effective agents for prophylaxis and treatment for both diseases . Medical advocacy for strengthening the Biological Weapons Convention, particularly with an enforceable protocol including verification and compliance provisions, is needed.

J Pharm Biomed Anal, 2002 Jun 20, 29(1-2), 183 - 93
Development and application of an analytical method for the determination of squalene in formulations of anthrax vaccine adsorbed; Spanggord RJ et al.; Specific lots of Anthrax Vaccine Adsorbed, administered to members of the US Armed Forces, have been described on various Internet sites and in news articles as a source of squalene, a chemical purported by these media to be associated with the Gulf War Syndrome . We have developed and validated a method using high-performance liquid chromatography with ultraviolet detection for the determination of squalene in anthrax vaccine preparations . The method has a limit of detection of 140 parts per billion and has been successfully applied to a commercial vaccine known to contain squalene . We have applied this method to 17 lots of Anthrax Vaccine Adsorbed administered to members of the US Armed Forces . No squalene has been detected in any lot . The results of these analyses provide direct evidence for the absence of squalene as an ingredient or a manufacturing contaminant in Anthrax Vaccine Adsorbed.

Psychol Rep, 2002 Apr, 90(2), 639 - 53
Self-reported changes in subjective health and anthrax vaccination as reported by over 900 Persian Gulf War era veterans; Schumm WR et al.; A 1999 study of United Kingdom servicemembers by Unwin, et al . recently found significant relationships between anthrax and other vaccinations, reactions to those vaccines, and later health problems for male current or former active military Gulf War veterans . Likewise, in 2000 Steele and in 1998 Gilroy found possible adverse effects of vaccinations on Gulf War veterans . However, the role of such vaccinations remains controversial; more recent government reports continue to dispute the existence of any data that might reflect adversely on the role of vaccinations on the health of Gulf War veterans . To address this controversy, the current study assessed similar relationships for over 900 Reserve Component Gulf War Era veterans from Ohio and nearby states . Gulf War veterans were more likely to report poorer health than non-Gulf veterans . Female veterans were more likely to report mild or severe reactions to vaccines than male veterans . Those veterans who received anthrax vaccine reported more reactions to vaccines than those who did not receive anthrax vaccine . Declines in long-term subjective health were associated with receipt of anthrax vaccine by Gulf War veterans but not for those who did not deploy to the Gulf, although few of the latter received anthrax vaccine . Regardless of deployment status, veterans who reported more severe reactions to vaccines were more likely to report declines in subjective health . Female veterans reported poorer health during the Gulf War than did male veterans, but sex was not related to veterans' reports of subjective health at subsequent times . It is recommended that servicemembers who experience severe reactions to anthrax vaccine be medically reevaluated before receiving further anthrax vaccine and that careful follow-ups be conducted of those receiving the vaccine currently, in accordance with Nass's 1999 recommendations . We also recommend that safer alternatives to thimerosal (a mercury sodium salt, 50% mercury) be used to preserve all vaccines.

An R Acad Nac Med (Madr), 2001, 118(4), 961 - 80
{Carbuncle (anthrax) as biological weapon}; Dominguez Carmona M; The authors explain the anthrax pathogeny as necessary base to treat the systemic anthrax, that it can be secondary to a terrorist aggression, that until now it causes death to damaged people . For fear that a contamination with anthracis spores by a terrorist aggression, it is imposed to administrate chymeprotection to damaged people, because once it is appeared the symptoms of the systemic illness, the antibiotics don't stop the process evolution . For that reason, we think it is important to know the process pathogeny, where it can be found the keys for effective treatment of carbuncle sepsis.

Clin Exp Rheumatol, 2002 Mar-Apr, 20(2), 217 - 20
Anthrax vaccination and joint related adverse reactions in light of biological warfare scenarios; Geier DA et al.; OBJECTIVES: The purpose of this analysis was to evaluate anthrax vaccine (AVA) and joint related adverse reactions based upon analysis of the VAERS database in light of the current possibility of the use of anthrax as a biological warfare agent . METHODS: A certified copy of the VAERS database was obtainedfrom the CDC . In this study, we conducted a retrospective analysis using Microsoft Access for all joint attributed adverse reactions reported following anthrax vaccination . The employment of chi-square analysis determined if the elevated incidence rates of associated adverse reactions in anthrax vaccine recipients were statistically significant . RESULTS: Our analysis shows a very large and statistically significant increase in joint symptoms following vaccination with AVA when compared to our control population consisting of adverse joint reactions reported following vaccination with hepatitis A vaccine and Td vaccine . CONCLUSION: We believe that civilian doctors need to become familiar with the adverse reactions that can be expected to follow the use of AVA . Both civilian and military doctors need to be vigilant in reporting all such reactions to VAERS, so that more information can be gathered about AVA . We also believe that an anthrax vaccine with an improved safety profile is needed if it is to be used in populations, either military or civilian, that are not under imminent threat of attack by biological warfare agents . It should also be kept in mind that the widespread use of anthrax vaccination may cause potential producers of biological weapons and terrorists to seek to produce anthrax strains that are not neutralized by the current vaccine.

Pharmacoepidemiol Drug Saf, 2002 Apr-May, 11(3), 189 - 202
Safety of anthrax vaccine: a review by the Anthrax Vaccine Expert Committee (AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS); Sever JL et al.; PURPOSE: To assess the safety of a licensed anthrax vaccine given to nearly 400,000 US military personnel, reports of adverse events (AEs) submitted to the Vaccine Adverse Event Reporting System (VAERS) were reviewed and evaluated medically . METHODS: The Anthrax Vaccine Expert Committee (AVEC), a civilian panel of private-sector physicians and other scientists, reviewed 602 VAERS reports using a Delphic approach (structured expert consensus) to assess the causal relationship between vaccination and the reported AEs and sought to identify unexpected patterns in the occurrence of medically important events . Reports were entered into a database and used to profile AEs with respect to person, type/location, relative frequency, severity/impact, concomitant illness or receipt of other drugs or vaccines, and vaccine lot . RESULTS: Nearly half the reports noted a local injection-site AE, with more than one-third of these involving a moderate to large degree of inflammation . Six events qualified as serious AEs (SAEs), and all were judged to be certain consequences of vaccination . Three-quarters of the reports cited a systemic AE (most common: flu-like symptoms, malaise, rash, arthralgia, headache), but only six individual medically important events were judged possibly or probably due to vaccine (aggravation of spondyloarthropathy (2), anaphylactoid reaction, arthritis (2), bronchiolitis obliterans organizing pneumonia) . CONCLUSIONS: Since some cases of local inflammation involved distal paresthesia, AVEC recommends giving subcutaneous injections of AVA over the inferior deltoid instead of the triceps to avoid compression injury to the ulnar nerve . At this time, ongoing evaluation of VAERS reports does not suggest a high frequency or unusual pattern of serious or other medically important AEs.

J Health Polit Policy Law, 2002 Apr, 27(2), 273 - 91
Responding to chemical, biological, or nuclear terrorism: the indirect and long-term health effects may present the greatest challenge; Hyams KC et al.; The possibility of terrorists employing chemical, biological, or nuclear/ radiological (CBN) materials has been a concern since 1995 when sarin gas was dispersed in a Tokyo subway . Contingency planning almost exclusively involved detection . containment, and emergency health care for mass casualties . However, it is clear that even small-scale CBN incidents--like the recent spread of anthrax spores through the mail--can cause widespread confusion, fear, and psychological stress that have lasting effects on the health of affected communities and on a nation's sense of well-being . More emphasis therefore needs to be placed on indirect effects and on the medical, social, economic, and legal consequences that follow months to years afterward . To respond effectively to CBN attacks, a comprehensive strategy needs to be developed that includes not only emergency response, but also long-term health care, risk communication, research, and economic assistance . Organizing an effective response challenges government institutions because the issues involved--eligibility for health care, the effects of low-level exposure to toxic agents . stress-related illnesses, unlicensed therapeutics . financial compensation--are complex and controversial.

Curr Infect Dis Rep, 2002 Jun, 4(3), 238 - 243
Inhalational Anthrax; Cullamar EK et al.; Until recently, inhalational anthrax was a medical curiosity in both the Western medical literature and clinical practice . The post-September 11, 2001 outbreak of this disease in the eastern United States that spread through the mail, however, instantly changed the appreciation of this disease and the appreciation of biological terrorism/warfare in general . The microbiology, epidemiology, clinical, and therapeutic/preventative aspects of this entity, classically known as "wool sorter's disease" are highlighted in this review.

Proc Natl Acad Sci U S A, 2002 May 14, 99(10), 7027 - 32
Mailborne transmission of anthrax: Modeling and implications; Webb GF et al.; A mathematical model is developed to analyze the transmission of inhalational anthrax through the postal system by cross-contamination of mail . The model consists of state vectors describing the numbers of cross-contaminated letters generated, the numbers of anthrax spores on these letters, the numbers of resulting infections in recipients, and matrices of transition probabilities acting on these vectors . The model simulates the recent outbreak in the United States, and provides a general framework to investigate the potential impact of possible future outbreaks.

Vaccine, 2002 May 22, 20(17-18), 2369 - 74
Monitoring anthrax vaccine safety in US military service members on active duty: surveillance of 1998 hospitalizations in temporal association with anthrax immunization; Sato PA et al.; We compared 1998 hospitalizations in active-duty US military personnel for possible temporal association with anthrax immunization . Immunization, demographic, and hospitalization data were analyzed using Cox proportional hazards modeling for hospitalization within 42 days of vaccination . Discharge diagnoses were aggregated into 14 International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) categories . Approximately 11% of subjects received one or more doses of vaccine during 1998; those immunized were more likely to be younger and male . Lower hospitalization rates were observed across doses and diagnostic categories among the immunized . Adjusted risk ratios for hospitalization by diagnostic category suggest that immunized service members were at equal or lesser risk for hospitalization than the non-immunized.

FEMS Microbiol Lett, 2002 Apr 9, 209(2), 301 - 5
Expression of anthrax lethal factor gene by osmolyte induction; Singh A et al.; The anthrax toxin consists of protective antigen (PA), lethal factor (LF) and edema factor (EF) . PA mediates the entry of LF and EF to the cytosol where they exert their effects . Although PA is the major component of the vaccines against anthrax, LF has also been found to play an important role in enhancing protective immunity . We have developed an osmolyte-inducible LF expression system . The protein expression system contributed no additional amino acids to the recombinant LF making it suitable for the human vaccine trials.

Nurs Manage . 2002 May;33(5):10, 11.
Our first line of defense against bioterrorism part 2; Simpson RL; In March, Part 1 of this two-part series examined the challenges with identifying bioterrorism-specifically the anthrax outbreak . Part 2 explains what's being done to equip America's health care providers to recognize and respond to future attacks, while protecting the public.

Proc Natl Acad Sci U S A, 2002 May 14, 99(10), 7049 - 53 Epub 2002 May 07.
Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigen; Cunningham K et al.; Assembly of anthrax toxin complexes at the mammalian cell surface involves competitive binding of the edema factor (EF) and lethal factor (LF) to heptameric oligomers and lower order intermediates of PA(63), the activated carboxyl-terminal 63-kDa fragment of protective antigen (PA) . We used sequence differences between PA(63) and homologous PA-like proteins to delineate a region within domain 1' of PA that may represent the binding site for these ligands . Substitution of alanine for any of seven residues in or near this region (R178, K197, R200, P205, I207, I210, and K214) strongly inhibited ligand binding . Selected mutations from this set were introduced into two oligomerization-deficient PA mutants, and the mutants were used in various combinations to map the single ligand site within dimeric PA(63) . The site was found to span the interface between two adjacent subunits, explaining the dependence of ligand binding on PA oligomerization . The locations of residues comprising the site suggest that a single ligand molecule sterically occludes two adjacent sites, consistent with the finding that the PA(63) heptamer binds a maximum of three ligand molecules . These results elucidate the process by which the components of anthrax toxin, and perhaps other binary bacterial toxins, assemble into toxic complexes.

Proc Natl Acad Sci U S A, 2002 May 14, 99(10), 7045 - 8 Epub 2002 May 07.
The lethal and edema factors of anthrax toxin bind only to oligomeric forms of the protective antigen; Mogridge J et al.; The three proteins that comprise anthrax toxin, edema factor (EF), lethal factor (LF), and protective antigen (PA), assemble at the mammalian cell surface into toxic complexes . After binding to its receptor, PA is proteolytically activated, yielding a carboxyl-terminal 63-kDa fragment (PA(63)) that coordinates assembly of the complexes, promotes their endocytosis, and translocates EF and LF to the cytosol . PA(63) spontaneously oligomerizes to form symmetric ring-shaped heptamers that are capable of binding three molecules of EF and/or LF as competing ligands . To determine whether binding of these ligands depends on oligomerization of PA(63), we prepared two oligomerization-deficient forms of this protein, each mutated on a different PA(63)-PA(63) contact face . In solution or when bound to receptors on Chinese hamster ovary K1 cells, neither mutant alone bound ligand, but a mixture of them did . After the two mutants were proteolytically activated and mixed with ligand in solution, a ternary complex was isolated containing one molecule of each protein . Thus EF and LF bind stably only to PA(63) dimers or higher order oligomers . These findings are relevant to the kinetics and pathways of assembly of anthrax toxin complexes.

ED Manag, 2002 May, 14(5), 52 - 4
Case study: ED acts quickly after anthrax; Expected adverse events in a mass smallpox vaccination campaign; Division of General Pediatrics, University of Michigan, Ann Arbor, USA . kempera@med.umich.edu

CONTEXT: Recent anthrax attacks in the United States have raised concern about the nation's vulnerability to a smallpox attack . Many strategies have been suggested to minimize the impact of such an attack, ranging from quarantine and vaccination of case contacts to resumption of routine vaccination . Before the latter strategy is adopted, an understanding of the likely consequences of mass vaccination is essential . COUNT: Number of adverse events resulting from two vaccination campaigns: vaccinating persons 1 to 29 years of age and vaccinating those 1 to 65 years of age . CALCULATION: Number of adverse events = incidence rate of adverse events x number vaccinated . We assumed 75% vaccine uptake in the target group (i.e., we estimated that about 25% of potential vaccine recipients would be excluded because they are, or have close contact with, individuals who have eczema or are immunocompromised) . DATA SOURCE: Historical data on the incidence of adverse events from smallpox vaccination were identified by a literature search . Number vaccinated was drawn from the January 2000 U.S . Census estimate . RESULTS: Fever (<1 case per 5 vaccine recipients) and rash (<1 case per 100 vaccine recipients) would be the most common adverse events . Serious adverse events, including encephalitis (<3 cases per million) and death (<2 cases per million), although rare, would be more common than with other currently recommended vaccines . After excluding high-risk individuals and their contacts, we estimate that a vaccination strategy directed at people aged 1 to 29 years would result in approximately 1600 serious adverse events and 190 deaths . Vaccinating people aged 1 to 65 years would result in approximately 4600 serious adverse events and 285 deaths . LIMITATIONS: While advances in health care over the past three decades could mitigate vaccine complications, the increased number of unimmunized high-risk individuals (e.g., those with eczema or immune suppression) could increase complication rates . CONCLUSIONS: The decision to resume smallpox vaccination depends on weighing the likelihood of a smallpox attack and its anticipated mortality against expected harm from a mass immunization program . Smallpox vaccine has a higher complication rate than any other vaccine currently being used . Careful prevaccination exclusion of high-risk individuals and their close contacts would be essential to minimize complications of a mass vaccination campaign, although such exclusions necessarily mean that some proportion of the population will remain susceptible to smallpox.

Am J Public Health, 2002 May, 92(5), 715 - 21
The Anthrax Vaccine Program: an analysis of the CDC's recommendations for vaccine use; Nass M; The anthrax vaccine was never proved to be safe and effective . It is one cause of Gulf War illnesses, and recent vaccinees report symptoms resembling Gulf War illnesses . The vaccine's production has been substandard . Without adequate evaluation, the Food and Drug Administration recently approved (retrospectively) significant changes made to the vaccine's composition since 1990 . The vaccine's mandatory use for inhalation anthrax is "off-label." A skewed review of the vaccine literature by the Centers for Disease Control and Prevention (CDC) led to remunerative collaborative research with the army, involving civilian volunteers . Despite acknowledging possible fetal harm, the CDC offered the vaccine to children and pregnant women . New trends could weaken prelicensure efficacy and safety review of medical products intended for biodefense and avoid manufacturer liability for their use.

AAOHN J, 2002 Apr, 50(4), 170 - 3
Anthrax attack at the United States Capitol . Front line thoughts; Anderson A et al.; One great fear was realized on October 15, 2001 when United States citizens witnessed firsthand the unprecedented release of anthrax into a community . Although the office of the Attending Physician to Congress had been preparing for such an unthinkable act, lessons were learned as the events unfolded . The following is a summary of the findings: Preparation, planning, and frequent review of bioterrorism response procedures are essential . Effective communication remains the key to successful team performance . Briefings conducted daily and on an as needed basis shape the progress and performance of the team members . Electronic mail may not necessarily be the most effective way to disseminate critical information because not everyone can access the Internet outside of the work environment . Setting up a call center for answering client's questions is crucial . Clients potentially exposed to anthrax should be evacuated from the immediate area . Testing is not indicated for everyone, only those in the immediate areas . Allow health care personnel to decide whom should be tested . Such health care decisions must not be made based on anxiety or expediency . A data collection template should be set up in advance . This template should include, at least, the following: name, date of birth, social security number, the physical location of where the client might have been exposed, antibiotics administered and dosage, test results, and home and work phone number . This should be networked so a group can access and update data in real time . If the occupational health clinic has its own pharmacy, have a pill counter available to help with antibiotic distribution . The team should meet several times daily to ensure dissemination of a reliable and consistent message to the clients . Team members should be prepared to review the medical aspects of anthrax with clients on a frequent basis . A website with updated information might prove helpful for those with Internet access . This experience provided a unique opportunity for the Office of the Attending Physician to Congress to put its bioterrorism plan into action . Nothing substitutes for preparedness . Communication was the most important tool because it kept the team informed and focused on the mission at hand . It behooves all occupational health nurses to begin preparing for future acts as extraordinary as the anthrax attack that occurred on October 15, 2001.

Dev Biol, 2002 May 15, 245(2), 348 - 61
Characterization of MPF and MAPK activities during meiotic maturation of Xenopus tropicalis oocytes; Bodart JF et al.; Resumption of meiosis in oocytes of Xenopus tropicalis required translation but not transcription, and was marked by the appearance of a white spot and a dark ring, coincident with entry into metaphase I and the onset of anaphase I, respectively . Cyclin B(2)/p34(cdc2) activity increased prior to the first meiotic division, declined at the onset of anaphase I, and subsequently increased again . The capacity of egg cytoplasm to induce germinal vesicle breakdown (GVBD) was inhibited by cycloheximide, despite the fact that these oocytes contained cyclin B(2)/p34(cdc2) complexes . However, cycloheximide-treated oocytes underwent GVBD following injection of constitutively active mitogen-activated protein kinase (MAPK) kinase 2 (MEK2), p33(Ringo), or Delta 90 cyclin B . MAPK activity increased just prior to the first meiotic division and remained stable thereafter . Although injection of constitutively active MEK2 induced GVBD, treatment with the MEK inhibitors U0126 or anthrax lethal factor delayed GVBD and prevented spindle formation . Interestingly, the ability of egg cytoplasm to induce GVBD was unaffected by the inhibition of MEK activity . Our results indicate that the synthesis of a novel or short-lived protein(s) which acts in a MEK-independent fashion is required in order for egg cytoplasm to induce GVBD in X . tropicalis oocytes.

Rev Sci Tech, 2002 Aug, 21(2), 359 - 83
Anthrax and wildlife; Hugh-Jones ME et al.; Although livestock anthrax is declining in many parts of the world, with an increasing number of countries probably truly free of the disease, anthrax remains enzootic in many national parks and even in some game ranching areas . These infected areas can present a persistent risk to surrounding livestock, which may otherwise be free of the disease, as well as a public health risk . The authors use as examples the national parks in southern Africa, the Wood Buffalo National Park in northern Alberta, Canada, and the deer ranching counties in south-west Texas, United States of America, to present the range of problems, epidemiology, and control procedures . While many advances have been achieved in the understanding of this disease, research is required into the genotypic grouping of anthrax isolates, improved field diagnostic techniques, and oral vaccines, as well as to provide a better understanding of spore survival in soil and the ecology of the disease under natural conditions.

Rev Sci Tech, 2002 Aug, 21(2), 249 - 63
Bacterial diseases of farmed deer and bison; Mackintosh C et al.; The most important aerobic bacterial diseases of farmed deer and bison include bovine tuberculosis, Johne's disease (paratuberculosis), yersiniosis, leptospirosis, brucellosis, pasteurellosis, anthrax, salmonellosis and colibacillosis . Anaerobic bacterial infections affecting the same animals include necrobacillosis and a number of clostridial diseases such as tetanus, blackleg, malignant oedema and pulpy kidney . The relative importance of these diseases will vary throughout the world according to timing and circumstance, but bovine tuberculosis and Johne's disease are likely to present the most significant problems with respect to diagnosis, control, trade in live animals and the establishment of wildlife reservoirs of infection . The authors summarise the aetiology, the principal species of animal affected, geographical distribution, transmission, clinical signs, pathology, diagnosis, treatment and control of these diseases.

Curr Opin Infect Dis, 2000 Apr, 13(2), 113 - 120
Current status of immunization against anthrax: old vaccines may be here to stay for a while; Turnbull PC; Anthrax vaccination has become a 'hot' topic . On the one hand, fears that Iraq holds secret caches of anthrax-based weaponry, that other countries may be developing or may have developed similar devices, or that hard-line groups may make their own anthrax-based devices for bioterrorist attacks have focused official attention on the need for means of protection, principally, though, for the military . On the other hand, the unsolved issues of the Gulf War illnesses have left elements of doubt in the minds of some as to the possible role of anthrax (among other) vaccines in this syndrome, and have drawn attention to the shortage of pre-clinical, clinical, pharmacological and safety data on the existing UK and US anthrax vaccines . In the middle are those hotly debating the US and Canadian policies of mandatory anthrax immunization for military personnel or, in the case of the UK policy of voluntary immunization, simply voting with their feet . Compounding matters have been the publicized failures of the US vaccine production facility and the less publicized UK problems of supply . Meanwhile, those in genuine at-risk occupations are left unsure whether, if they can get the vaccine at all, they really want it . Despite two decades of elegant science aimed at formulating alternative vaccines to overcome all the problems of efficacy, safety and supply, such an alternative is at least five years away, and the current status is that we must live with the old vaccines or not vaccinate.

Proc Natl Acad Sci U S A, 2002 Apr 16, 99(8), 5241 - 6
Human antibodies against spores of the genus Bacillus: a model study for detection of and protection against anthrax and the bioterrorist threat; Zhou B et al.; A naive, human single-chain Fv (scFv) phage-display library was used in bio-panning against live, native spores of Bacillus subtilis IFO 3336 suspended in solution . A direct in vitro panning and enzyme-linked immunosorbent assay-based selection afforded a panel of nine scFv-phage clones of which two, 5B and 7E, were chosen for further study . These two clones differed in their relative specificity and affinity for spores of B . subtilis IFO 3336 vs . a panel of spores from 11 other Bacillus species/strains . A variety of enzyme-linked immunosorbent assay protocols indicated these scFv-phage clones recognized different spore epitopes . Notably, some spore epitopes markedly changed between the free and microtiter-plate immobilized state as revealed by antibody-phage binding . An additional library selection procedure also was examined by constructing a Fab chain-shuffled sublibrary from the nine positive clones and by using a subtractive panning strategy to remove crossreactivity with B . licheniformis 5A24 . The Fab-phage clone 52 was improved compared with 5B and was comparable to 7E in binding B . subtilis IFO 3336 vs . B . licheniformis 5A24, yet showed a distinctive crossreactivity pattern with other spores . We also developed a method to directly detect individual spores by using fluorescently labeled antibody-phage . Finally, a variety of "powders" that might be used in deploying spores of B . anthracis were examined for antibody-phage binding . The strategies described provide a foundation to discover human antibodies specific for native spores of B . anthracis that can be developed as diagnostic and therapeutic reagents.

Proc Natl Acad Sci U S A, 2002 Apr 16, 99(8), 5237 - 40
Early statistical detection of anthrax outbreaks by tracking over-the-counter medication sales; Goldenberg A et al.; The recent series of anthrax attacks has reinforced the importance of biosurveillance systems for the timely detection of epidemics . This paper describes a statistical framework for monitoring grocery data to detect a large-scale but localized bioterrorism attack . Our system illustrates the potential of data sources that may be more timely than traditional medical and public health data . The system includes several layers, each customized to grocery data and tuned to finding footprints of an epidemic . We also propose an evaluation methodology that is suitable in the absence of data on large-scale bioterrorist attacks and disease outbreaks.

J Okla State Med Assoc, 2002 Apr, 95(4), 281 - 5
Oklahoma City and Tulsa Metropolitan Medical Response System; Sacra JC et al.; The tragic loss of lives on September 11 followed by the Anthrax contaminations reinforced the need for work already underway through the Metropolitan Medical Response System (MMRS) . Through leadership from the Medical Director for the Medical Control Board and EMSA, Oklahoma City and Tulsa have been the beneficiaries of nearly $1.5 million dollars in funding to prepare for nuclear, chemical or bioterrorism . The two Oklahoma cities were among the second wave of cities invited in 1999 to participate in the federally funded program for Metropolitan Medical Response . Many of the requirements of the contract have already been met under the capable guidance of Michael Murphy, a 23 year paramedic with 12 years of management experience with EMSA . Among the plans completed or underway are a Development Plan, MMRS System Plan, Forward Movement of Patients Plan, Pre-hospital Response Plan, a Biological Incident Plan, a Hospital Response Plan, a Training Plan and an Equipment and Pharmaceutical Plan . Coordinated planning between the two cities bring the added benefit of seamless sharing of personnel between both ends of the turnpike should a disaster impact one rather than both communities.

Physician Exec, 2002 Mar-Apr, 28(2), 80 - 3
Managing terror . Public health officials learn lessons from bioterrorism attacks; Benjamin GC; When a photo-journalist presented with the first case of inhalation anthrax in the United States in 23 years, it marked the worse case of biological terrorism in our nation's history . It also marked a significant management challenge for numerous local, state and federal officials . Review what was learned and how we can better prepare for future attacks.

Cell, 2002 Mar 22, 108(6), 739 - 42
Calmodulin in action: diversity in target recognition and activation mechanisms; Hoeflich KP et al.; Recent structural studies on calmodulin complexes with anthrax adenylyl cyclase and rat Ca2+-activated K+ channel have uncovered unexpected ways by which calmodulin interacts with target proteins.

J Am Acad Nurse Pract, 2001 Apr, 13(4), 164 - 8; quiz 169-70
Inhalational anthrax: threat, clinical presentation, and treatment; Henry L; PURPOSE: To provide nurse practitioners (NPs) with a basic understanding of clinical presentation, transmission, diagnosis, pharmacological treatment, and post-exposure prophylaxis of inhalational anthrax . DATA SOURCES: Selected research and clinical articles and government guidelines . CONCLUSIONS: Inhalational anthrax has an incubation period of 1 to 6 days and is very difficult to diagnose early . The chest radiograph consistently reveals a widened mediastinum and pleural effusion without infiltrates . Mortality for inhalational anthrax is high, despite aggressive treatment after onset of symptoms . Delays in diagnosis contribute to the high mortality rate . IMPLICATIONS FOR PRACTICE: The potential use of aerosolized anthrax as a biological warfare weapon has renewed interest in inhalational anthrax . Primary care providers are cornerstones in the defense against biological weapons because they may be the first to recognize and report suspicious cases.

Vestn Ross Akad Med Nauk, 2002, (2), 3 - 6
{Affinity sorbents having magnetic properties in the clinical picture and diagnosis of communicable and non-communicable diseases}; Pokrovskii VI et al.; Affine magnetic sorbents which have no analogs in the practice of our country have been for the first time developed for the rapid diagnosis of various life-threatening diseases (plague, cholera, anthrax, glanders, meliodosis, tularemia, leptospirosis, dysentery, viral hepatitis A) and for the identification of their causative agents . The efficacy of new magnet-controlling test systems has been repeatedly confirmed by their applications in epidemiological events and emergencies: in the epidemiological surveillance of viral hepatitis A in Stavropol and in the Caucasian Mineralnye Vody towns, Stavropol Territory (1994), in the identification of cholera patients, in the detection of transmission factors, when monitoring during large epidemic out-bursts of cholera in Stavropol (1990), Daghestan (1994), as well as in the microbiological monitoring during military conflicts in the Chechen Republic (1995) . The application of the sorbents has shown that their sensitivity is 4-5 times as much as that of conventional serological assays . In addition, biotechnologies for the production of polyacrylamide and composite aluminosilicate affine immunosorbents with magnetic properties have been developed . They have been used as the basis for designing immobilized granulated antigen reagents for the immunodiagnosis, differential diagnosis, evaluation of the time course and severity of a disease, the efficiency of therapy in patients with systemic scleroderma, proliferative arthritis, systemic lupus erythematosus, juvenile rheumatoid arthritis, osteochondrosis.

Nurs Manage, 2002 Mar, 33(3), 10 - 3
Our first line of defense against bioterrorism . Part 1; Simpson RL; Health care's response to the anthrax outbreak highlights our critical need to enlist sophisticated information technology (IT) tools in the defense against bioterrorism . Part 1 of a two-part series explains what went wrong in the most recent attack and suggests how a national IT infrastructure might help in the future.

Mod Healthc, 2002 Feb 25, 32(8), 8 - 9, 12
20/20 hindsight . Months after anthrax claimed the lives of several . Americans, hospitals review their reaction to the event--and plan for future crises; Becker C; Last fall, after a nation suffered the unthinkable attacks of Sept . 11, a second wave of terror held Americans in its grip . Questions still surround a series of baffling cases of anthrax that shook New York and Connecticut . Each of the hospitals involved report that despite the unsolved mysteries posed by these events, they are more cautious and better-prepared for future bioterrorism attacks.

JAMA, 2002 Mar 27, 287(12), 1556 - 60
Relationship between prepregnancy anthrax vaccination and pregnancy and birth outcomes among US Army women; Wiesen AR et al.; CONTEXT: Substantial concern surrounds the potential health effects of the anthrax vaccine, particularly the potential adverse effects on reproductive processes . OBJECTIVE: To determine whether receipt of anthrax vaccination by reproductive-aged women has an effect on pregnancy rates . DESIGN, SETTING, AND PATIENTS: Cohort study, based on information from a computer database, of women aged 17 to 44 years who were stationed at Fort Stewart, Ga, or Hunter Army Airfield, Ga, from January 1999 through March 2000 . MAIN OUTCOME MEASURES: Pregnancy and birth rates and adverse birth outcomes . RESULTS: Of a total of 4092 women, 3136 received at least 1 dose of the anthrax vaccine . There was a total of 513 pregnancies, with 385 following at least 1 dose of anthrax vaccine . The pregnancy rate ratio (before and after adjustment for marital status, race, and age) comparing vaccinated with unvaccinated women was 0.94 (95% confidence interval {CI}, 0.8-1.2; P =.60) . There were 353 live births and 25 pregnancies lost to follow-up . The birth odds ratio after anthrax vaccination (before and after adjustment for marital status and age) was 0.9 (95% CI, 0.5-1.4; P =.55) . After adjusting for age, the odds ratio for adverse birth outcome after receiving at least 1 dose of anthrax vaccination was 0.9 (95% CI, 0.4-2.4; P =.88) . However, this study did not have sufficient power to detect adverse birth outcomes . CONCLUSION: Anthrax vaccination had no effect on pregnancy and birth rates or adverse birth outcomes.

J Occup Environ Med, 2002 Mar, 44(3), 271 - 81
Risk factors for multisymptom illness in US Army veterans of the Gulf War; Wolfe J et al.; This research study examined the prevalence of symptoms and identified risk factors for reported symptoms among a group of Army Gulf War (GW) veterans . A survey was mailed to all members of the Ft . Devens cohort in 1997, representing the third assessment of a group that consisted of 2949 US Army soldiers deployed to the Gulf, and was studied initially in 1991 . A total of 1290 subjects responded to the mailed survey; aggressive follow-up methods to address non-response bias were employed . Subjects were classified as having multisymptom illness if they reported symptoms from at least two of three symptom categories (fatigue, mood-cognition, musculoskeletal) . Sixty percent of the respondents met criteria for multisymptom illness . Female gender, lower levels of education, psychological symptoms, self-reported use of a medical clinic in the Gulf, ingestion of anti-nerve gas pills (pyridostigmine bromide), anthrax vaccination, tent heaters, exposure to oil fire smoke, and chemical odors were significantly related to multisymptom illness in logistic regression analyses . Analyses in which subjects were stratified by level of psychological symptoms revealed different sets of GW-service environmental exposures and suggest that subgroups of GW veterans may have different sets of risk factors.

Mil Med, 2002 Mar, 167(3), 205 - 10
Ambulatory medical visits among anthrax-vaccinated and unvaccinated personnel after return from southwest Asia; Rehme PA et al.; The Department of Defense launched a mandatory anthrax immunization program for military personnel in December 1997 . This program has been criticized for many reasons, including concern over side effects . This study was designed to give a quick answer to the question of whether vaccinated persons who deployed to southwest Asia were more likely to seek medical care upon their return than their unvaccinated counterparts . The results demonstrated that there was no greater risk for vaccinated persons to have a diagnosis recorded in the Ambulatory Data System (0.96 RR) than unvaccinated persons . In addition, there was no significant increased risk for a recorded diagnosis in any 1 of the 17 International Classification of Diseases, Ninth Revision, categories or for 16 specific adverse health conditions.

Health Aff (Millwood), 2002 Mar-Apr, 21(2), 78 - 93
The case for more active policy attention to health promotion . To succeed, we need leadership that informs and motivates, economic incentives that encourage change, and science that moves the frontiers; McGinnis MJ et al.; Until recently, when anthrax triggered a concern about preparedness in the public health infrastructure, U.S . health policy and health spending had been dominated by a focus on payment for medical treatment . The fact that many of the conditions driving the need for treatment are preventable ought to draw attention to policy opportunities for promoting health . Following a brief review of the determinants of population health-genetic predispositions, social circumstances, environmental conditions, behavioral patterns, and medical care-this paper explores some of the factors inhibiting policy attention and resource commitment to the nonmedical determinants of population health and suggests approaches for sharpening the public policy focus to encourage disease prevention and health promotion.

Harv Bus Rev, 2002 Feb, 80(2), 55 - 60, 127
Managing emotional fallout . Parting remarks from America's top psychiatrist . Interview by Diane Coutu; Hyman SE; Last fall, the United States was brutally thrust into a new and dangerous world . As the twin towers of the World Trade Center collapsed and the Pentagon burned, the horrible reality of terrorism seared the American consciousness . It touched more than the victims and their families; everyone who sat transfixed before the horrific images on TV lived through the trauma . In a sense, we were all eyewitnesses, and we must all cope with feelings of anger, stress, and anxiety . That poses a huge immediate challenge for business, because it is largely in the workplace--where we spend so many of our waking hours--that we will confront these emotions . And many companies have risen to the challenge, establishing new guidelines for processing mail in light of anthrax fears and organizing stress reduction programs for employees . While the logic of taking such action is incontestable, it raises a much larger question: What responsibility does a company bear for the mental well-being of its work-force? If companies help employees deal with depression and anxiety in the wake of terrorist acts, doesn't that put mental health care on the business agenda? To answer these questions, HBR senior editor Diane Coutu talked with Dr . Steven Hyman, the former director of the National Institute for Mental Health . In this interview, he discusses the implications of coping with tragedy, the resilience of individuals, and the treatment of mental illness . And he suggests that September 11, 2001, may come to be seen as a tipping point--the moment when managers started to think about dealing with mental health issues on a regular basis.

Euro Surveill, 2001 Nov, 6(11), 166 - 71
Deliberate releases of biological agents: initial lessons for Europe from events in the United States; Harling R et al.; The experience of autumn 2001, when anthrax spores were released in the postal system, had considerable consequences in the United States and in Europe . The threat of covert deliberate releases against civilians has become a reality . In Europe, despite the growing number of criminal hoaxes, no cases of anthrax linked to deliberate releases have been reported, and the only contaminated letters were addressed to American embassies abroad . Nevertheless, the time has come for Europe to set up efficient and timely plans to respond to bioterrorism, under the coordination of the European Commission.

Euro Surveill, 2001 Nov, 6(11), 159 - 66
Bioterrorism preparedness and response in European public health institutes; Coignard B; Members of the Eurosurveillance editorial board; The terrorist attacks on 11 September 2001 and the deliberate release of anthrax in the United States had consequences for public health not only there, but also in Europe . Europe's public health systems had to manage numerous postal materials possibly contaminated with anthrax . Our survey aimed to document the response of European public health institutes to recent bioterrorist events to identify the gaps that need to be addressed; 18 institutes from 16 countries participated in this Euroroundup . Bioterrorist threats in Europe were hoaxes only, and should be considered as a "preparedness exercise" from which three lessons can be drawn . Firstly, because of inadequate preparedness planning and funding arrangements, Europe was not ready in October 2001 to respond to bioterrorism . Secondly, although European institutes reacted quickly and adapted their priorities to a new type of threat, they need adequate and sustained support from national governments to maintain their overall capacity . Thirdly, the recent crisis demonstrated the need for increased investment in epidemiology training programmes and the establishment of a technical coordination unit for international surveillance and outbreak response in the European Union.

Biochem Biophys Res Commun, 2002 Mar 22, 292(1), 41 - 4
TNF receptor 1, IL-1 receptor, and iNOS genetic knockout mice are not protected from anthrax infection; Kalns J et al.; Anthrax produces at least two toxins that cause an intense systemic inflammatory response, edema, shock, and eventually death . The relative contributions of various elements of the immune response to mortality and course of disease progression are poorly understood . We hypothesized that knockout mice missing components of the immune system will have an altered response to infection . Parent strain mice and knockouts were challenged with LD95 of anthrax spores (5 x 10(6)) administered subcutaneously . Our results show that all genetic knockouts succumbed to anthrax infection at the same frequency as the parent . TNF antibody delayed death but TNF receptor 1 knockout had no effect . IL-1 receptor or iNOS knockouts died sooner . Anthrax was more abundant in the injection site of TNF-alpha and iNOS knockouts compared to parent suggesting that attenuated cellular response increases rate of disease progression . With the exception of edema and necrosis at the injection site pathological changes in internal organs were not observed . (C)2002 Elsevier Science (USA).

Int J Med Microbiol, 2002 Feb, 291(6-7), 411 - 7
Discovery of the anthrax toxin: the beginning of studies of virulence determinants regulated in vivo; Smith H; Anthrax kills many animal species . It was used to prove Koch's Postulates in 1876 . Soon after that the classical bacterial toxins were produced in vitro, but up to 1950, a lethal toxin had not been demonstrated in either anthrax bacilli or filtrates from laboratory cultures . The cause of death had been an enigma for seventy years . During the 1950's, a toxin was recognized by examining bacteria and their products obtained from guinea pigs dying of anthrax . The toxin was found in their plasma and shown to contain two components . It was then produced in vitro and a third component recognized . The work reawakened interest in bacterial toxins after a period of dormancy and showed that toxins could be multicomponent . It demonstrated that previously unknown determinants of bacterial pathogenicity could be revealed by examining organisms grown in vivo . It was the beginning of such studies, which took a long time to evolve, but have now expanded greatly with the development of many new methods for examining bacterial activities in vivo . This paper is a personal account of the early work.

J Am Med Inform Assoc, 2002 Mar-Apr, 9(2), 120 - 2
The space race and biodefense: lessons from NASA about big science and the role of medical informatics; Wagner MM; The events that followed the launch of Sputnik on Oct 4, 1957, provide a metaphor for the events that are following the first bioterroristic case of pulmonary anthrax in the United States . This paper uses that metaphor to elucidate the nature of the task ahead and to suggest questions such as, Can the goals of the biodefense effort be formulated as concisely and concretely as the goal of the space program? Can we measure success in biodefense as we did for the space project? What are the existing resources that are the equivalents of propulsion systems and rocket engineers that can be applied to the problems of biodefense?

Pediatr Dermatol, 2002 Jan-Feb, 19(1), 36 - 8
Traditions, anthrax, and children; Ciftci E et al.; Anthrax is sporadically seen in Turkey, especially among people who live in rural areas and who come in contact with animals . Two siblings with cutaneous anthrax are described in this report . A week before their admission to the hospital, contaminated cow's blood was smeared on their foreheads as part of a traditional ritual . Both children were successfully treated with crystalline penicillin . In developing countries, traditions such as blood smearing may be an important factor in the transmission of anthrax to children.

J Biol Chem, 2002 May 3, 277(18), 16249 - 56 Epub 2002 Feb 21.
Uncoupling of the cholera toxin-G(M1) ganglioside receptor complex from endocytosis, retrograde Golgi trafficking, and downstream signal transduction by depletion of membrane cholesterol; Wolf AA et al.; To induce toxicity, cholera toxin (CT) must first bind ganglioside G(M1) at the plasma membrane, enter the cell by endocytosis, and then traffic retrograde into the endoplasmic reticulum . We recently proposed that G(M1) provides the sorting motif necessary for retrograde trafficking into the biosynthetic/secretory pathway of host cells, and that such trafficking depends on association with lipid rafts and lipid raft function . To test this idea, we examined whether CT action in human intestinal T84 cells depends on membrane cholesterol . Chelation of cholesterol with 2-hydroxypropyl beta-cyclodextrin or methyl beta-cyclodextrin reversibly inhibited CT-induced chloride secretion and prolonged the time required for CT to enter the cell and induce toxicity . These effects were specific to CT, as identical conditions did not alter the potency or toxicity of anthrax edema toxin that enters the cell by another mechanism . We found that endocytosis and trafficking of CT into the Golgi apparatus depended on membrane cholesterol . Cholesterol depletion also changed the density and specific protein content of CT-associated lipid raft fractions but did not entirely displace the CT-G(M1) complex from these lipid raft microdomains . Taken together these data imply that cholesterol may function to couple the CT-G(M1) complex with raft domains and with other membrane components of the lipid raft required for CT entry into the cell.

Med Tr Prom Ekol, 2002, (1), 15 - 7
{Role of hormonal factors in pulmonary angiopathy development during anthrax-silicosis}; Abushakhmanova AKh; The article represents results of radionuclide study of hormonal levels and pulmonary microcirculation in anthracosilicosis . The authors discuss mechanisms underlying influence of vasoactive hormones on pulmonary microcirculation . The authors revealed relationships between hormonal and vascular disorders in anthracosilicosis.

J Assoc Acad Minor Phys, 2002 Jan, 13(1), 19 - 22
Vaccines for adults in an age of terrorism; Simberkoff MS; Vaccines are an effective, safe, and relatively inexpensive means of preventing infection; thus, they are important tools for fighting biological terrorism . Two diseases, anthrax and smallpox, for which vaccines are not available to the general public are discussed . Three other vaccines--tetanus toxoid, influenza vaccine, and hepatitis B vaccine--generally recommended for adults, may be in short supply as a result of recent acts of terrorism.

JAMA, 2002 Feb 20, 287(7), 869 - 74
Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7-month-old infant; Freedman A et al.; A 7-month-old infant with cutaneous anthrax developed severe systemic illness despite early treatment with antibiotics . The infant displayed severe microangiopathic hemolytic anemia with renal involvement, coagulopathy, and hyponatremia . These findings are unusual with cutaneous anthrax, but have been described in illness resulting from spider toxin and may delay correct diagnosis . The systemic manifestations of the disease persisted for nearly a month despite corticosteroid therapy, but resolved.

Ann Pharmacother, 2002 Feb, 36(2), 334 - 7
Anthrax: safe treatment for children; Benavides S et al.; Information regarding the treatment of anthrax infection is scarce in adults and is even more limited in children . Children, however, may be at a greater risk for developing an infection and systemic disease if exposed to anthrax than adults . The Centers for Disease Control and Prevention (CDC) recommends the use of doxycycline or ciprofloxacin for prophylaxis and treatment in children . Doxycycline currently is not indicated for use in children < 8 years old, due to staining of teeth and inhibition of bone growth associated with tetracyclines . Doxycycline, however, may have less adverse effect on teeth than its precursors . Ciprofloxacin has a pediatric indication only when a child is potentially exposed to inhaled anthrax . Ciprofloxacin is contraindicated in pediatric patients because fluoroquinolones were shown to cause cartilage toxicity in immature animals . Although children of various ages have received ciprofloxacin, there are few reports of cartilage toxicity . Because anthrax is a potentially fatal infection, the benefits to using these antibiotics greatly outweigh the risks . Therefore, the use of these antibiotics in children can be recommended, despite the lack of adequate efficacy and safety studies in pediatric patients with anthrax.

J Am Osteopath Assoc, 2002 Jan, 102(1), 41 - 3
Symptoms associated with anthrax exposure: suspected "aborted" anthrax; Cymet TC et al.; Anthrax is a naturally occurring organism with a low incidence of infection . There are no known cases of human-to-human transmission . Bioterrorism-related anthrax in the United States has been seen in three high-risk groups: (1) postal workers, (2) politicians and their staffs, and (3) the press . It appears as though the bioterrorism-related anthrax cases of fall 2001 have been transmitted through the US Postal Service . The authors present a case in which a person at high risk for anthrax exposure was inadequately treated and had symptoms that do not fall into any specific category of disease . It emphasizes the need for someone who has been started on prophylaxis for anthrax to complete a full 60-day course of treatment . It also shows the effectiveness of antibiotic therapy, even in those with high exposure to weaponized anthrax . Further, we would like to suggest that there may exist a new clinical entity of "aborted anthrax infection."

Otolaryngol Head Neck Surg, 2002 Jan, 126(1), 8 - 13
Anthrax: ENT manifestations and current concepts; Wirtschafter A et al.; In light of recent events, anthrax has once again taken center stage in the world of science and the world in which we live . Because patients with anthrax may initially present to otolaryngology clinics, it is important for the otolaryngologist to know how to diagnose and treat this entity . This article will present current information on epidemiology, microbiology, pathogenesis/clinical manifestations, diagnosis, and treatment with a particular interest in the head and neck region.

Radiology, 2002 Feb, 222(2), 305 - 12
Inhalational anthrax after bioterrorism exposure: spectrum of imaging findings in two surviving patients; Earls JP et al.; The radiographic and computed tomographic (CT) findings in two patients with documented inhalational anthrax resulting from bioterrorism exposure are presented . Chest radiographs demonstrated mediastinal widening, adenopathy, pleural effusions, and air-space disease . Chest CT images revealed enlarged hyperattenuating mediastinal and hilar lymph nodes and edema of mediastinal fat . Chest CT findings are helpful for making the initial diagnosis . To the authors' knowledge, the spectrum and follow-up of CT findings have not been previously described.

Vaccine, 2002 Jan 31, 20(9-10), 1412 - 20
Anthrax vaccine: immunogenicity and safety of a dose-reduction, route-change comparison study in humans; Pittman PR et al.; Anthrax vaccine adsorbed (AVA), an effective countermeasure against anthrax, is administered as six subcutaneous (SQ) doses over 18 months . To optimize the vaccination schedule and route of administration, we performed a prospective pilot study comparing the use of fewer AVA doses administered intramuscularly (IM) or SQ with the current schedule and route . We enrolled 173 volunteers, randomized to seven groups, who were given AVA once IM or SQ; two doses, 2 or 4 weeks apart, IM or SQ; or six doses at 0, 2, 4 weeks and 6, 12, and 18 months (control group, licensed schedule and route) . IM administration of AVA was associated with fewer injection site reactions than SQ administration . Following the first SQ dose of AVA, compared to males, females had a significantly higher rate of injection site reactions such as erythema, induration and subcutaneous nodules (P<0.001) . Reaction rates decreased with a longer dose interval between the first two doses . The peak anti-PA IgG antibody response of subjects given two doses of AVA 4 weeks apart IM or SQ was comparable to that seen among subjects who received three doses of AVA at 2-week intervals . The IM route of administering this aluminum hydroxide adsorbed vaccine is safe and has comparable peak anti-PA IgG antibody levels when two doses are administered 4 weeks apart compared to the licensed initial dose schedule of three doses administered 2 weeks apart . A large pivotal study is being planned by the Centers for Disease Control and Prevention to confirm these results.

Salud Publica Mex, 2001 Nov-Dec, 43(6), 604 - 13
{The ABCs on anthrax for health personnel}; Valdespino-Gomez JL et al.; The purpose of this series of articles is to present to health personnel an updated summary on bioterrorism associated agents . In this first article an updated summary on anthrax is presented . Emphasis has been placed on the characteristics of cases which occurred during October in the United States of America and on the experience of governmental agencies of that country to face the emergency . Measures implemented in Mexico are described as well . The authors are convinced that the best arm against terror is timely and updated information.

Biochemistry, 2002 Feb 5, 41(5), 1445 - 50
PA63 channel of anthrax toxin: an extended beta-barrel; Nassi S et al.; Anthrax toxin consists of three protein components: protective antigen (PA), lethal factor (LF), and edema factor (EF) . PA(63), generated by protease "nicking" of whole PA, is responsible for delivering the toxin's catalytic fragments (LF and EF) to the target cell's cytosol . In planar bilayer membranes, trypsin-nicked PA makes cation-selective voltage-gated channels with a pore diameter of > or =12 A . The channels are presumed to be heptameric "mushrooms", with an extracellular "cap" region and a membrane-inserted, beta-barrel "stem" . Although the crystal structure of the water-soluble monomeric form has been resolved to 2.1 A and that of the heptameric "prepore"" to 4.5 A, the structure for the membrane-bound channel (pore) has not been determined . We have engineered mutant channels that are cysteine-substituted in residues in the putative beta-barrel, and identified the residues lining the channel lumen by their accessibility to a water-soluble sulfhydryl-specific reagent . The reaction with lumen-exposed cysteinyl side chains causes a drop in channel conductance, which we used to map the residues that line the pore . Our results indicate that the beta-barrel structure extends beyond the bilayer and involves residues that are buried in the monomer . The implication is that major rearrangement of domains in the prepore cap region is required for membrane insertion of the beta-barrel stem.

J Infect Dis, 2002 Jan 15, 185(2), 244 - 51 Epub 2002 Jan 03.
Delivery of exogenous protein antigens to major histocompatibility complex class I pathway in cytosol; Cao H et al.; A fragment of anthrax lethal factor possesses the interesting function of delivering recombinant protein antigens through the classical major histocompatibility complex (MHC) class I pathway . This region of the lethal factor lacks the domain associated with anthrax cytotoxicity and functions independently of its binary partner, protective antigen . Experiments that used inhibitors at different steps of the MHC class I pathway supported this hypothesis . Application of this discovery to current T cell assays allows for the measurement of cytotoxic T lymphocyte function without resorting to live vectors and provides a useful new tool to design and test T cell-dependent vaccines.

Nature, 2002 Jan 24, 415(6870), 396 - 402
Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin; Drum CL et al.; Oedema factor, a calmodulin-activated adenylyl cyclase, is important in the pathogenesis of anthrax . Here we report the X-ray structures of oedema factor with and without bound calmodulin . Oedema factor shares no significant structural homology with mammalian adenylyl cyclases or other proteins . In the active site, 3'-deoxy-ATP and a single metal ion are well positioned for catalysis with histidine 351 as the catalytic base . This mechanism differs from the mechanism of two-metal-ion catalysis proposed for mammalian adenylyl cyclases . Four discrete regions of oedema factor form a surface that recognizes an extended conformation of calmodulin, which is very different from the collapsed conformation observed in other structures of calmodulin bound to effector peptides . On calmodulin binding, an oedema factor helical domain of relative molecular mass 15,000 undergoes a 15 A translation and a 30 degrees rotation away from the oedema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation . These allosteric changes provide the first molecular details of how calmodulin modulates one of its targets.

Physician Exec, 2002 Jan-Feb, 28(1), 59 - 62
We are all in this together . Terrorism and the physician executive; Bottles K; The threat of bioterrorism striking America is no longer a threat . It's real . Take a look at how the anthrax-laced letters and future acts of terrorism impact physician executives . Also consider some ways to prepare your physicians for a bioterrorism emergency.

Mil Med, 2002 Jan, 167(1), 74 - 5
Delayed-type hypersensitivity reaction to anthrax vaccine; Greidanus TG et al.; The Anthrax Vaccine Immunization Program is a Department of Defense initiative to protect military personnel against the threat of anthrax . Surveillance for adverse events associated with anthrax vaccination has shown that mild local reactions are not uncommon while systemic reactions are extremely rare . We present a case of 26-year-old male with delayed-type hypersensitivity after two doses of anthrax vaccine.

Biochemistry, 2002 Jan 22, 41(3), 1079 - 82
Stoichiometry of anthrax toxin complexes; Mogridge J et al.; After being proteolytically activated, the protective antigen (PA) moiety of anthrax toxin self-associates to form symmetric, ring-shaped heptamers . Heptameric PA competitively binds the enzymatic moieties of the toxin, edema factor and lethal factor, and translocates them across the endosomal membrane by a pH-dependent process . We used two independent approaches to determine how many of the seven identical EF/LF binding sites of the PA heptamer can be occupied simultaneously . We measured isotope ratios in complexes assembled from differentially radiolabeled toxin subunits, and we determined the molecular masses of unlabeled complexes by multiangle laser light scattering . Both approaches yielded the same value: the PA heptamer in solution binds three molecules of protein ligand under saturating conditions . This suggests that each bound ligand sterically occludes the binding sites of two PA subunits . According to this model, a ligand-saturated heptamer is asymmetric, with the sites of six of the seven subunits occluded . These results contribute to the conceptual framework for understanding the mechanism of membrane translocation by anthrax toxin.

J Ky Med Assoc, 2001 Dec, 99(12), 528 - 32
What I need to know about anthrax today; Harris RD et al.; The US Department of Defense has been concerned about the use of anthrax as a biological weapon by an enemy on US troops for a number of years . This is the reason why the military has embarked on a vaccination program for its forces deployed to regions of the world, which are considered high-risk areas . These areas have been in the Southwest Asia-Persian Gulf region as well as the Korean Peninsula . Many intelligence personnel have also been concerned about the possibility of biological agents being used by terrorists in the Continental United States . The recent anthrax incidents in Florida and elsewhere in the United States have significantly heightened concerns along these lines, especially following the terrorist attacks on the World Trade Center and the Pentagon on September 11th . The death of a Florida businessman, identification of infection in one of his co-workers, evidence of exposure and in some instances, cutaneous infection in some others, as well as evidence of contamination in their buildings, raised further concerns of the possibility of terrorist activity using biological warfare in this country . It is somewhat ironic that a disease that you probably haven't heard about since medical school has become the focus of national attention . Our goal in this communication is to refresh your understanding of what anthrax is and what you need to know about it today since anthrax is counted among the weapons of mass destruction . As a member of the medical profession, you will need to know what to look for in patients and how to treat them if they are contaminated with this biological agent . You will also have to serve as the "front line" of the public health system and alert the police and public health agencies.

MMWR Morb Mortal Wkly Rep, 2001 Aug 17, 50(32), 677 - 80
Human anthrax associated with an epizootic among livestock--North Dakota, 2000; Supply chain vulnerable in many ways; The specter of terrorism has reached the materials management department, now that a supply room worker in a New York hospital has died from anthrax . At the same time, the tragedy of the Sept . 11 attacks has led hospitals and their vendors to realize that "partnership" is not just a trendy word for business association anymore; it is a strategy for survival.

Ophthalmology, 2002 Jan, 109(1), 99 - 104
Optic neuritis after anthrax vaccination; Kerrison JB et al.; OBJECTIVE: To report the occurrence of optic neuritis after anthrax vaccination in two patients . DESIGN: Observational case reports, review of literature . METHODS: Description of clinical history, examination, neuroimaging, and further studies in two patients experiencing optic neuritis in temporal association with anthrax vaccination . MAIN OUTCOME MEASURES: Visual acuity, visual fields . RESULTS: Two patients, 39 and 23 years of age, were seen with acute optic neuritis 1 month and 2 weeks, respectively, after anthrax booster vaccination and successfully treated with intravenous methylprednisolone . The first patient had a typical presentation and course of unilateral retrobulbar optic neuritis with excellent visual recovery . The second patient had a bilateral anterior optic neuritis and has required chronic immunosuppression to maintain his vision . Retinal and optic nerve autoantibodies were present in the second patient . No cross-reactive epitopes between anthrax vaccine and retina/optic nerve were identified . CONCLUSION: Optic neuritis is a potential adverse reaction of anthrax vaccination.

MMWR Morb Mortal Wkly Rep, 2001 Dec 7, 50(48), 1077 - 9
Update: Investigation of bioterrorism-related anthrax--Connecticut, 2001.
{Female patient with cutaneous anthrax in Belgium}
Gyssens IC, Weyns D, Kullberg BJ, Ursi JP.

Erasmus MC Universitair Medisch Centrum, afd . Medische Microbiologie & Infectieziekten, Postbus 2040, 3000 CA Rotterdam . gyssens@bacl.azr.nl

A 23-year-old Turkish woman was admitted with an infection of the left thumb . The clinical picture was typical for cutaneous anthrax . Microbiological tests confirmed the diagnosis 'infection by Bacillus anthracis' . She recovered when treated with penicillin, although later tests revealed that the bacteria were resistant to this antibiotic . The patient became infected in Belgium as a result of wounding herself on the teeth of an illegally slaughtered sheep, which had possibly become infected in the pasture . Recognising the characteristic clinical picture of cutaneous anthrax is essential for prompt treatment and a favourable prognosis.

ED Manag, 2001 Dec, 13(12), 133 - 6
Are you ready for anthrax, or worse? You must revamp your bioterrorism plan.
{Anthrax and carbuncle}
Arrese JE, Pierard-Franchimont C, Pierard GE.

Service de Dermatopathologie, Universite de LiegeAnthrax is a name given in French language to two distinct infectious diseases . One corresponds to carbuncle which is a collection of boils . The other one corresponds to the English term anthrax . This condition has a clinical presentation and an outcome that vary according to the inoculation site being cutaneous, pulmonary or digestive, and to the bacterial and toxin spread in the body.

Mod Healthc, 2001 Nov 19, 31(47), 4 - 5, 16
How much is enough? AHA, lawmakers debate federal funding for bioterrorism preparation; Lovern E; The anthrax outbreak was just the beginning . Recently the nation's hospitals got their first taste of dealing with a bioterrorism attack . And as fears of different terrorist onslaughts escalate, healthcare providers struggle to answer questions they never faced before--and to anticipate new ones.

Teratology, 2001, 64 Suppl 1, S26 - 9
The Department of Defense Birth Defects Registry: overview of a new surveillance system; Ryan MA et al.; BACKGROUND: The U.S . Department of Defense (DoD) is challenged with monitoring and protecting the health and wellbeing of its service members . The growing number of women on active duty and the diverse hazardous exposures associated with military service make reproductive health issues a special concern of DoD . To address this concern, the DoD Birth Defects Registry was established at the DoD Center for Deployment Health Research located at the Naval Health Research Center, San Diego, California . METHODS: The registry captures comprehensive data on healthcare utilization to calculate the prevalence of birth defects in the children of military beneficiaries . Population-based electronic surveillance is supplemented by active case validation efforts . RESULTS: Since its establishment in 1998, the registry has captured data on more than 90,000 births that occur in military families each year . Detailed analyses, to include linking registry data with military occupational exposure data (e.g., anthrax vaccination), are underway . CONCLUSIONS: The DoD Birth Defects Registry provides important reproductive health information on the geographically dispersed military population . This program is expected to complement civilian public health programs and be especially valuable to military members and their families.

Bull Hist Med, 2001 Winter, 75(4), 771 - 81
Edwin Klebs's Grundversuche; Carter KC; In 1876, discussions of the role of microorganisms in disease causation focused on anthrax and wound infections, and even in respect to these diseases there was controversy . In a series of papers on the pathologicality of bacteria, Edwin Klebs identified four "Grundversuche" (fundamental tests) that provided a basis for his own research strategy . The Grundversuche can be read as the following hypotheses: first, all bacteria are pathological; second, bacteria never occur spontaneously; third, every disease is caused only by bacteria; and fourth, the bacteria that cause distinguishable disease are distinguishable . Although some of these hypotheses are literally false, together they constitute part of a rational basis for a bacterial theory of disease, and, as such, they mark a true revolution in etiological thought.

Vaccine, 2001 Dec 12, 20(5-6), 789 - 96
Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by immunization with dendritic cells treated with an anthrax toxin fusion protein; Moriya O et al.; As a novel and safe vaccine strategy, the anthrax toxin-mediated antigen delivery system composed of lethal factor (LF) fusion protein and protective antigen (PA) has been studied to prime hepatitis C virus (HCV) core-specific cytotoxic T lymphocytes (CTLs) in vivo . The core epitope fused to LF (LF-core) together with PA induces a negligible core-specific CTL response in mice, whereas core-specific CTL are effectively primed in mice by injecting dendritic cells (DCs) treated in vitro with LF-core and PA . These findings imply that LF fusion protein plus PA in combination with dendritic cells may be useful for a novel T cell vaccine against HCV infection.

Mod Healthc, 2001 Nov 5, 31(45), 4 - 5, 11
'We're all working together.' New York-area hospitals redouble efforts in face of anthrax death; Becker C; The death of a New York hospital worker from inhalation anthrax last week put new strains on an overburdened public health system . The fact that no source of the bacteria could be found only added to the difficulties . Hospitals along the East Coast battled clinical, logistical and financial problems from the outbreak.

MMWR Morb Mortal Wkly Rep, 2001 Nov 16, 50(45), 1008 - 10
Update: Investigation of bioterrorism-related anthrax, 2001; Update: Investigation of bioterrorism-related anthrax and adverse events from antimicrobial prophylaxis; CDC and state and local public health authorities continue to investigate cases of bioterrorism-related anthrax . As of November 7, a total of 22 cases of anthrax have been identified according to the CDC surveillance case definition; 10 were confirmed inhalational anthrax cases and 12 cases (seven confirmed and five suspected) were cutaneous anthrax (Table 1) . The majority of cases have occurred in persons working at postal facilities in New Jersey (NJ) and the District of Columbia (DC) in which letters contaminated with anthrax were handled or processed using high-speed sorting machines, or at media companies in New York City (NYC) or Florida (FL) where letters, either confirmed or presumed to be contaminated with anthrax, were opened or handled . The probable exposures for a case of cutaneous anthrax in NJ and a case of inhalational anthrax in NYC remain unknown . Epidemiologic investigations of these cases and surveillance to detect new cases of bioterrorism-associated anthrax continue . This report updates the investigation of these cases and describes adverse events associated with antimicrobial prophylaxis.

JAMA, 2001 Nov 28, 286(20), 2554 - 9
Death due to bioterrorism-related inhalational anthrax: report of 2 patients; Borio L et al.; On October 9, 2001, a letter containing anthrax spores was mailed from New Jersey to Washington, DC . The letter was processed at a major postal facility in Washington, DC, and opened in the Senate's Hart Office Building on October 15 . Between October 19 and October 26, there were 5 cases of inhalational anthrax among postal workers who were employed at that major facility or who handled bulk mail originating from that facility . The cases of 2 postal workers who died of inhalational anthrax are reported here . Both patients had nonspecific prodromal illnesses . One patient developed predominantly gastrointestinal symptoms, including nausea, vomiting, and abdominal pain . The other patient had a "flulike" illness associated with myalgias and malaise . Both patients ultimately developed dyspnea, retrosternal chest pressure, and respiratory failure requiring mechanical ventilation . Leukocytosis and hemoconcentration were noted in both cases prior to death . Both patients had evidence of mediastinitis and extensive pulmonary infiltrates late in their course of illness . The durations of illness were 7 days and 5 days from onset of symptoms to death; both patients died within 24 hours of hospitalization . Without a clinician's high index of suspicion, the diagnosis of inhalational anthrax is difficult during nonspecific prodromal illness . Clinicians have an urgent need for prompt communication of vital epidemiologic information that could focus their diagnostic evaluation . Rapid diagnostic assays to distinguish more common infectious processes from agents of bioterrorism also could improve management strategies.

JAMA, 2001 Nov 28, 286(20), 2549 - 53
Clinical presentation of inhalational anthrax following bioterrorism exposure: report of 2 surviving patients; Mayer TA et al.; The use of anthrax as a weapon of biological terrorism has moved from theory to reality in recent weeks . Following processing of a letter containing anthrax spores that had been mailed to a US senator, 5 cases of inhalational anthrax have occurred among postal workers employed at a major postal facility in Washington, DC . This report details the clinical presentation, diagnostic workup, and initial therapy of 2 of these patients . The clinical course is in some ways different from what has been described as the classic pattern for inhalational anthrax . One patient developed low-grade fever, chills, cough, and malaise 3 days prior to admission, and then progressive dyspnea and cough productive of blood-tinged sputum on the day of admission . The other patient developed progressively worsening headache of 3 days' duration, along with nausea, chills, and night sweats, but no respiratory symptoms, on the day of admission . Both patients had abnormal findings on chest radiographs . Non-contrast-enhanced computed tomography of the chest showing mediastinal adenopathy led to a presumptive diagnosis of inhalational anthrax in both cases . The diagnoses were confirmed by blood cultures and polymerase chain reaction testing . Treatment with antibiotics, including intravenous ciprofloxacin, rifampin, and clindamycin, and supportive therapy appears to have slowed the progression of inhalational anthrax and has resulted to date in survival.

Curr Biol, 2001 Nov 13, 11(22), R905 - 6
Anthrax: a motor protein determines anthrax susceptibility; Hanna PC; A new study has found that polymorphisms in the host gene kif1C, which encodes a kinesin-like motor protein, determine whether mouse macrophages are resistant or sensitive to anthrax lethal toxin . These findings may lead the way to discovering how both germ and host factors might contribute to a lethal infection.

J Biol Chem, 2002 Jan 25, 277(4), 3006 - 10 Epub 2001 Nov 19.
Mapping the anthrax protective antigen binding site on the lethal and edema factors; Lacy DB et al.; Entry of anthrax edema factor (EF) and lethal factor (LF) into the cytosol of eukaryotic cells depends on their ability to translocate across the endosomal membrane in the presence of anthrax protective antigen (PA) . Here we report attributes of the N-terminal domains of EF and LF (EF(N) and LF(N), respectively) that are critical for their initial interaction with PA . We found that deletion of the first 36 residues of LF(N) had no effect on its binding to PA or its ability to be translocated . To map the binding site for PA, we used the three-dimensional structure of LF and sequence similarity between EF and LF to select positions for mutagenesis . We identified seven sites in LF(N) (Asp-182, Asp-187, Leu-188, Tyr-223, His-229, Leu-235, and Tyr-236) where mutation to Ala produced significant binding defects, with H229A and Y236A almost completely eliminating binding . Homologous mutants of EF(N) displayed nearly identical defects . Cytotoxicity assays confirmed that the LF(N) mutations impact intoxication . The seven mutation-sensitive amino acids are clustered on the surface of LF and form a small convoluted patch with both hydrophobic and hydrophilic character . We propose that this patch constitutes the recognition site for PA.

Nature, 2001 Nov 8, 414(6860), 229 - 33
Crystal structure of the anthrax lethal factor; Pannifer AD et al.; Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax . It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways . Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2 . LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage . Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition . Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II . Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I . The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity.

MMWR Morb Mortal Wkly Rep, 2001 Oct 19, 50(41), 893 - 7
Recognition of illness associated with the intentional release of a biologic agent; Centers for Disease Control and Prevention; On September 11, 2001, following the terrorist incidents in New York City and Washington, D.C., CDC recommended heightened surveillance for any unusual disease occurrence or increased numbers of illnesses that might be associated with the terrorist attacks . Subsequently, cases of anthrax in Florida and New York City have demonstrated the risks associated with intentional release of biologic agents . This report provides guidance for health-care providers and public health personnel about recognizing illnesses or patterns of illnessthat might be associated with intentional release of biologic agents.

Yeni Tip Tarihi Arastirmalari, 1995, 1, 91 - 7
{Zoeros Pasha's report presented to the Sultinate on his return from Paris}; Yildirim N; The Ottoman Empire dispatched a committee consisting of Zoeros Pasha, the president, Dr . Huseyin remzi and veterinarian Huseyin Husnu, who were members sent to learn how the method of the vaccination of rabies was practiced in Paris in 1886 . Zoeros Pasha relates their studies in Paris, as well as his idea on the novelties he observed there and comments on the advantages of them in case of application in the Empire, in his report dated December 29th of 1886, prepared on his return from Paris . Zoeros Pasha and Huseyin Hsnu Bey learned the vaccination practice, attending Pasteur's laboratory . Zoeros Pasha studied bacteriology for three months and Huseyin Remzi attended the laboratory of "Jardin des Plantes" in order to do some zoological researches . When Pasteur went on vacation, Zoeros Pasha provided for Husnu Bey to attend the Veterinary School of Paris and directed his attention to the anthrax vaccination found by Pasteur . Huseyin Hsnu Bey and Dr . Huseyin Remzi Bey composed a book based on their translations on the subject Zoeros Pasha also mentions in his report the following topics on which he says he could report, if desired: 1 . New methods of treatment applied for heart and lung diseases . 2 . The most effective prophylactic methods and sanitary precautions on the epidemic and infectious diseases . 3 . Improvement planned for the Imperial School of Medicine . 4 . Use of anatomy in finding out criminals, in order to help the police forces.

Curr Biol, 2001 Oct 2, 11(19), 1503 - 11
Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor; Watters JW et al.; BACKGROUND: Inbred mouse strains exhibit striking differences in the susceptibility of their macrophages to the effects of anthrax lethal toxin (LeTx) . Previous data has shown that this difference in susceptibility lies downstream of toxin entry into macrophages . A locus controlling this phenotype, called Ltxs1, has been mapped to chromosome 11, but the responsible gene has not been identified . RESULTS: Here, we report the identification of the Ltxs1 gene as Kif1C, which encodes a kinesin-like motor protein of the UNC104 subfamily . Kif1C is the only gene in the Ltxs1 interval exhibiting polymorphisms between susceptible and resistant strains . Multiple alleles of Kif1C determine the susceptibility or resistance of cultured mouse macrophages to LeTx . Treatment of resistant macrophages with brefeldin-A (which alters the cellular localization of Kif1C) induces susceptibility to LeTx, while ectopic expression of a resistance allele of Kif1C in susceptible macrophages causes a 4-fold increase in the number of cells surviving LeTx treatment . We also show that cleavage of map kinase kinase 3, a target of LeTx proteolysis, occurs in resistant cells . CONCLUSIONS: We conclude that mutations in Kif1C are responsible for the differences in the susceptibility of inbred mouse macrophages to LeTx and that proper Kif1C function is required for LeTx resistance . Since the LeTx-mediated proteolysis of map kinase kinase 3 occurs even in resistant cells, Kif1C does not affect cellular entry or processing of LeTx and likely influences events occurring later in the intoxication pathway.

Nat Biotechnol, 2001 Oct, 19(10), 958 - 61
Designing a polyvalent inhibitor of anthrax toxin; Mourez M et al.; Screening peptide libraries is a proven strategy for identifying inhibitors of protein-ligand interactions . Compounds identified in these screens often bind to their targets with low affinities . When the target protein is present at a high density on the surface of cells or other biological surfaces, it is sometimes possible to increase the biological activity of a weakly binding ligand by presenting multiple copies of it on the same molecule . We isolated a peptide from a phage display library that binds weakly to the heptameric cell-binding subunit of anthrax toxin and prevents the interaction between cell-binding and enzymatic moieties . A molecule consisting of multiple copies of this nonnatural peptide, covalently linked to a flexible backbone, prevented assembly of the toxin complex in vitro and blocked toxin action in an animal model . This result demonstrates that protein-protein interactions can be inhibited by a synthetic, polymeric, polyvalent inhibitor in vivo.

J Biol Chem, 2001 Dec 7, 276(49), 46326 - 32 Epub 2001 Sep 26.
Inhibition of axotomy-induced neuronal apoptosis by extracellular delivery of a Bcl-XL fusion protein; Liu XH et al.; Bcl-2 and Bcl-XL prevent neuronal apoptosis during development, neurodegenerative disease, and trauma . To test a new anti-apoptosis strategy for neuroprotection, we engineered nontoxic components of anthrax toxin into a Bcl-XL delivery system . Delivery of Bcl-XL by this system prevented apoptosis of cultured rat cerebellar granule cells and macrophages, and the prevention depended on both the Bcl-XL and the anthrax toxin receptor binding/translocation moieties . Furthermore, neuronal death in vivo in a retinal ganglion cell model of axotomy-induced apoptosis was inhibited by administration of this fusion protein . Thus, Bcl-XL protein can be delivered into cells from the medium or interstitial space, offering a new way to block apoptosis upstream of many caspases and the mitochondria dysfunction phase of apoptosis.

Clin Lab Med, 2001 Sep, 21(3), 513 - 48, ix
Clinicopathologic aspects of bacterial agents; Martin GJ et al.; Bacteria were the first organisms recognized for their potential as agents of bioaggression and the possibility of their use by a terrorist or rogue nation is considered a significant threat . Five of the more likely agents (anthrax, plague, tularemia, Q fever, and brucellosis) are reviewed with emphasis on their epidemiology, clinical presentation, diagnosis, and pathology . Particular emphasis is given to the presentation of the diseases as they may appear after use in a biowarfare scenario.

AIDS Res Hum Retroviruses, 2001 Sep 1, 17(13), 1257 - 64
Robust HIV type 2 cellular immune response measured by a modified anthrax toxin-based enzyme-linked immunospot assay; Sarr AD et al.; Evaluation of immune mechanisms responsible for control of viral replication is critical to understanding HIV-2 attenuated biological characteristics in pathogenesis and transmission . Evaluation of the cellular immune response is often based on labor-intensive techniques that limit the scope of most studies performed . A simple and rapid anthrax toxin-based ELISPOT method to assess HIV-2 cellular immune response was developed . The modified anthrax toxin-based antigen presentation process performed better than a recombinant vaccinia system and the ELISPOT method significantly enhanced the ease and simplicity of the assay . Using this method, a robust HIV-2 cellular immune response directed toward the p26 core protein was exhibited in 21 of 24 (87.5%) infected women, and all 8 seronegative subjects were negative in both assays . Cellular immune responses were associated with low HIV-2 viral load . This simple and rapid modified anthrax toxin-based ELISPOT method allowed us to demonstrate, strong cellular immune responses that may be critical determinants in the HIV-2 attenuated phenotype.

J Appl Microbiol, 2001 Sep, 91(3), 435 - 41
Detection of anthrax spores in endemic regions of northern Canada; Dragon DC et al.; AIMS: To determine the level of anthrax spore contamination in endemic regions of northern Canada between outbreaks . METHODS AND RESULTS: Bacterial endospores were extracted from specimens via flotation and cultured on selective PLET medium . Of 588 environmental specimens collected, 11 (1.9%) contained viable anthrax spores . CONCLUSION: High environmental concentrations of anthrax spores in northern Canada appear limited to scavenger faeces and anthrax carcass sites . Burial and cremation appear equally effective at removing anthrax spores from the immediate environment, though cremation may be improved by re-burning cremation sites containing unburned animal hair . SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes an effective anthrax spore detection system . It provides the first bacteriological evidence that mammalian scavengers can disseminate anthrax spores in northern Canada, and its results may be compared with future environmental studies of untreated anthrax carcass sites to help improve government response plans.

Biochem Biophys Res Commun, 2001 Sep 21, 287(2), 542 - 9
Hydrophobic residues Phe552, Phe554, Ile562, Leu566, and Ile574 are required for oligomerization of anthrax protective antigen; Ahuja N et al.; Anthrax protective antigen (PA) plays a central role in facilitating the entry of active toxin components, namely, lethal factor and edema factor, into the cells . PA is also the main immunogen of both human and veterinary vaccine against anthrax . During host cell intoxication, protective antigen binds to the receptors on cell surface, gets proteolytically activated, oligomerizes to form a heptamer and binds to lethal factor or edema factor . The complex, formed by binding of lethal factor or edema factor to oligomerized PA, is internalized by receptor-mediated endocytosis . Acidification of the endosome results in the insertion of the heptamer into the membrane, thereby forming a pore through which lethal factor or edema factor can translocate into the cytosol . In this study we have identified hydrophobic residues, Phe552, Phe554, Ile562, Leu566, and Ile574, which are required for oligomerization of anthrax protective antigen . Mutation of these conserved residues to alanine impaired the oligomerization of protective antigen . Consequently, these mutants became nontoxic in combination with lethal factor and edema factor . Therapeutic importance of these mutants and their potential as vaccine candidates is discussed .

Natl Med J India, 2001 Jul-Aug, 14(4), 225 - 30
Bioterrorism: a threat for which we are ill prepared; Dhawan B et al.; Of the weapons of mass destruction, the biological ones are the most feared and bioterrorism has become one of the most vicious threats to civilized society in recent times . Biological weapons have been sporadically used for centuries . Despite international regulations, there has been a global re-emergence of the threat of biological warfare . As many as 17 countries are suspected of either including or developing biological agents in their weapons programmes . In the past decade, a number of terrorist organizations with access to bioweapons technology have emerged . Current surveillance systems may be inadequate to detect biological attacks . The onset of illness is often delayed, thus the timing and location of such an event may be extremely difficult to identify . We are unfamiliar with most of the agents of biological warfare and are ill-equipped to handle the consequences of such an attack . In addition, there is no apparent coherent policy to handle a biological terrorist incident . Given the enormity of what is possible in the event of a biological attack, we must be prepared to detect, diagnose, epidemiologically characterize and respond appropriately to biological weapons . Of the potential biological weapons, smallpox and anthrax pose the greatest threats.

Biol Chem, 2001 Jun, 382(6), 941 - 6
Participation of residue F552 in domain III of the protective antigen in the biological activity of anthrax lethal toxin; Khanna H et al.; The protective antigen (PA) component of anthrax toxin translocates the catalytic moieties lethal factor (LF) and edema factor (EF) into the cytosol . The proteolytically activated 63 kDa form of PA (PA63) has the ability to oligomerize and bind LF/EF . PA has four distinct domains performing specialized functions; whereas the function of domains I, II and IV has been well characterized, domain III has no known role in the biological activity of PA . Here we report the role of amino acid residues lining an exposed hydrophobic patch of domain III in the biological activity of PA . The residues Phe552, Phe554, lIe562, Leu566 and lle574 were individually substituted with alanine and the effect was studied . All mutant PA proteins except Phe552Ala were equally active as wild-type PA in exhibiting a toxic phenotype to J774A.1 cells in the presence of LF . Substitution of Ala for Phe552 reduced the ability of PA to intoxicate cells by more than 250-fold . However, Phe552Ala was equally active in receptor binding and susceptibility to trypsin and chymotrypsin as wild-type PA, the activities that have been shown to be essential for the biological activity of PA . This mutated PA protein had a decreased ability to bind LF, oligomerize on cells and to induce release of 86Rb+ from Chinese hamster ovary cells . These results suggest that the residue Phe552 in PA plays an important role in LF binding and oligomerization . Our study provides a basis for further exploration of the biological significance of domain III of PA.

Biochem Biophys Res Commun, 2001 Aug 10, 286(1), 6 - 11
Rapid purification of recombinant anthrax-protective antigen under nondenaturing conditions; Ahuja N et al.; Anthrax-protective antigen is the central moiety of the anthrax toxin complex that mediates the entry of the other two toxin components, lethal factor and edema factor into the cells . It is also the main immunogen of the cell-free vaccine against anthrax . However, in addition to PA, the vaccine contains trace amounts of other culture-derived proteins that contribute to the side effects of the vaccine like pain, edema, erythrema, etc . Thus there is a need to develop high-resolution purification methods to purify PA to homogeneity . In this study we have presented a purification strategy for rapid purification of recombinant protective antigen under nondenaturing conditions, which ensures that not only biological activity but also the conformational integrity of immunological epitopes is well-preserved . The protein was purified to homogeneity in a two-step purification procedure that takes just 6 h for completion . Three milligrams of recombinant protective antigen obtained from 1-liter culture was comparable to B . anthracis protective antigen in terms of functional and biological activity . Moreover, the immunogenicity elicited by the purified protein in mice was also studied . The studies reported here are part of continuing research that aims to provide a safe and efficacious alternative to the current vaccine against anthrax .

Eur J Ophthalmol, 2001 Apr-Jun, 11(2), 171 - 4
Palbebral anthrax; Celebi S et al.; PURPOSE: Anthrax is a rare infection transmitted to humans from animals or animal products . In cutaneous anthrax it may produce lesions of the eyelids which can lead to cicatricial ectropion . METHODS: We examined three women and five men with anthrax of the eyelids . Intravenous penicillin G was used alone as therapy . RESULTS: All patients presented with a localized itchy erythematous papule of the eyelid . A necrotising ulcer formed in each case, resulting in black eschar . The lesions resolved, with only mild cicatrization of the eyelid in all the patients . CONCLUSIONS: Anthrax is primarily an infectious disease of domestic animals but it is also seen in humans . Eyelids are rarely affected but cutaneous anthrax should be considered in any patient with a painless ulcer or black eschar who has a history of exposure to animals.

Br J Dermatol, 2001 Jul, 145(1), 146 - 50
Cowpox virus in a 12-year-old boy: rapid identification by an orthopoxvirus-specific polymerase chain reaction; Schupp P et al.; Although smallpox was eradicated 20 years ago, other members of the genus Orthopoxvirus (OPV), such as cowpox virus (CPXV) or monkeypox virus, are still a threat to humans . Because human CPXV infection is rare, it is seldom suspected on clinical grounds only . We report a boy who presented with two necrotic ulcers with surrounding erythema . Infection with OPV was suspected, as antibiotic treatment had not produced improvement and smears were negative for anthrax . An OPV was isolated and an OPV-specific polymerase chain reaction combined with a subsequent restriction enzyme fragment length polymorphism assay confirmed infection by CPXV . Although the patient's cat had had no skin lesions, OPV-specific antibodies were found at a titre of 1 : 8 in a plaque reduction assay, suggesting that the cat had transmitted the virus to the boy.

Curr Infect Dis Rep, 2001 Jun, 3(3), 249 - 257
Pulmonary Manifestations of Bioterrorism; Heddurshetti R et al.; Along with smallpox, inhalation anthrax and pneumonic plague are among the diseases most likely to be spread by biowarfare, either from a rogue nation or terrorist group . Neither anthrax nor plague has been seen by many pulmonary (or any other) physicians in the United States . This article summarizes these two diseases as pulmonary manifestations of bioterrorism and discusses the possibility of avian influenza as a potential respiratory pathogen in biowarfare . It is hoped that phyisicians will need to know this information only as an academic exercise and not because of a clinical circumstance.

Am J Public Health, 2001 May, 91(5), 710 - 6
Hospital preparedness for victims of chemical or biological terrorism; Wetter DC et al.; OBJECTIVES: This study examined hospital preparedness for incidents involving chemical or biological weapons . METHODS: By using a questionnaire survey of 224 hospital emergency departments in 4 northwestern states, we examined administrative plans, training, physical resources, and representative medication inventories . RESULTS: Responses were received from 186 emergency departments (83%) . Fewer than 20% of respondent hospitals had plans for biological or chemical weapons incidents . About half (45%) had an indoor or outdoor decontamination unit with isolated ventilation, shower, and water containment systems, but only 12% had 1 or more self-contained breathing apparatuses or supplied air-line respirators . Only 6% had the minimum recommended physical resources for a hypothetical sarin incident . Of the hospitals providing quantitative answers about medication inventories, 64% reported sufficient ciprofloxacin or doxycycline for 50 hypothetical anthrax victims, and only 29% reported sufficient atropine for 50 hypothetical sarin victims (none had enough pralidoxime) . CONCLUSIONS: Hospital emergency departments generally are not prepared in an organized fashion to treat victims of chemical or biological terrorism . The planned federal efforts to improve domestic preparedness will require substantial additional resources at the local level to be truly effective.

Science, 2001 Apr 27, 292(5517), 695 - 7
Dominant-negative mutants of a toxin subunit: an approach to therapy of anthrax; Sellman BR et al.; The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes . We identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and block its ability to translocate the enzymic moieties across membranes . These mutants strongly inhibited toxin action in cell culture and in an animal intoxication model, suggesting that they could be useful in therapy of anthrax.

Microbiol Immunol, 2001, 45(2), 119 - 25
Role of furin in delivery of a CTL epitope of an anthrax toxin-fusion protein; Zhang Y et al.; Anthrax toxin lethal factor (LF) in combination with anthrax toxin protective antigen (PA) was endocytosed and translocated to the cytosol of mammalian cells . Residues 1-255 of anthrax toxin lethal factor (LFn) was fused to a cytotoxic T lymphocyte (CTL) epitope of an influenza virus . For processing the toxins, PA must be cleaved into a 63-kDa fragment (PA63) by furin, which is a subtilisin-like processing endo-protease expressed by many eukaryotic cells . To test the ability of cells treated with the LFn fusion protein plus PA to deliver the epitope, CTL assay was performed . Two types of cell lines were identified, one was able to deliver CTL epitope while the other failed to efficiently deliver the epitope . To further elucidate the differences between these cells, the role of furin in these cells was examined . Disruption of the furin gene reduced its ability to deliver the CTL epitope . Furin expression in cells capable of efficiently delivering CTL epitope was quantitatively higher than in cells unable to deliver the epitope . The results suggest that furin plays a critical role in delivery of the CTL epitope of LFn fusion protein.

Infect Immun, 2001 May, 69(5), 2888 - 93
Search for correlates of protective immunity conferred by anthrax vaccine; Reuveny S et al.; Vaccination by anthrax protective antigen (PA)-based vaccines requires multiple immunization, underlying the need to develop more efficacious vaccines or alternative vaccination regimens . In spite of the vast use of PA-based vaccines, the definition of a marker for protective immunity is still lacking . Here we describe studies designed to help define such markers . To this end we have immunized guinea pigs by different methods and monitored the immune response and the corresponding extent of protection against a lethal challenge with anthrax spores . Active immunization was performed by a single injection using one of two methods: (i) vaccination with decreasing amounts of PA and (ii) vaccination with constant amounts of PA that had been thermally inactivated for increasing periods . In both studies a direct correlation between survival and neutralizing-antibody titer was found (r(2) = 0.92 and 0.95, respectively) . Most significantly, in the two protocols a similar neutralizing-antibody titer range provided 50% protection . Furthermore, in a complementary study involving passive transfer of PA hyperimmune sera to naive animals, a similar correlation between neutralizing-antibody titers and protection was found . In all three immunization studies, neutralization titers of at least 300 were sufficient to confer protection against a dose of 40 50% lethal doses (LD(50)) of virulent anthrax spores of the Vollum strain . Such consistency in the correlation of protective immunity with anti-PA antibody titers was not observed for antibody titers determined by an enzyme-linked immunosorbent assay . Taken together, these results clearly demonstrate that neutralizing antibodies to PA constitute a major component of the protective immunity against anthrax and suggest that this parameter could be used as a surrogate marker for protection.

Acta Ophthalmol Scand, 2001 Apr, 79(2), 208 - 9
Anthrax as the cause of preseptal cellulitis and cicatricial ectropion; Soysal HG et al.; A 54-year-old female farmer with anthrax infection of the eyelids is presented . She was initially managed with high dose intravenous penicillin G treatment . Following complete healing of the eyelid lesions, significant cicatricial ectropion resulted . Her right lower eyelid ectropion was corrected by surgical reconstruction using full thickness skin graft after a period of 6 months during which the cicatrization process stabilized . Satisfactory cosmetic and functional improvement was achieved . Anthrax of the eyelid must be considered in the differential diagnosis of preseptal or orbital cellulitis and any reconstructive procedure should be attempted only after the cessation of the healing process.

J Biol Chem, 2001 May 25, 276(21), 17976 - 84 Epub 2001 Mar 12.
Targeting of tumor cells by cell surface urokinase plasminogen activator-dependent anthrax toxin; Liu S et al.; Urokinase plasminogen activator receptor (uPAR) binds pro-urokinase plasminogen activator (pro-uPA) and thereby localizes it near plasminogen, causing the generation of active uPA and plasmin on the cell surface . uPAR and uPA are overexpressed in a variety of human tumors and tumor cell lines, and expression of uPAR and uPA is highly correlated to tumor invasion and metastasis . To exploit these characteristics in the design of tumor cell-selective cytotoxins, we constructed mutated anthrax toxin-protective antigen (PrAg) proteins in which the furin cleavage site is replaced by sequences cleaved specifically by uPA . These uPA-targeted PrAg proteins were activated selectively on the surface of uPAR-expressing tumor cells in the presence of pro-uPA and plasminogen . The activated PrAg proteins caused internalization of a recombinant cytotoxin, FP59, consisting of anthrax toxin lethal factor residues 1-254 fused to the ADP-ribosylation domain of Pseudomonas exotoxin A, thereby killing the uPAR-expressing tumor cells . The activation and cytotoxicity of these uPA-targeted PrAg proteins were strictly dependent on the integrity of the tumor cell surface-associated plasminogen activation system . We also constructed a mutated PrAg protein that selectively killed tissue plasminogen activator-expressing cells . These mutated PrAg proteins may be useful as new therapeutic agents for cancer treatment.

Biotechnol Appl Biochem, 2001 Apr, 33(Pt 2), 71 - 4
Anthrax-toxin-mediated delivery of a 19 kDa antigen of Mycobacterium tuberculosis into the cytosol of mammalian cells; Mehra V et al.; PA63, the proteolytically activated 63 kDa fragment of protective antigen (PA, 83 kDa), mediates translocation of lethal factor (LF) and oedema factor into the cytosol . The N-terminal 254 amino acids of LF (LFn) are required for binding to PA63 and mediating translocation of active ligands fused to either the N- or C-terminus . Here we report translocation of a 19 kDa antigen of Mycobacterium tuberculosis into the cytosol of mammalian cells when fused to the C-terminus of LFn (LFn-19kDa) . The fusion protein was non-toxic to J774A.1 macrophage cells in combination with PA and retained the ability to bind to PA63 when incubated with Chinese hamster ovary K1 cells . The data show the efficacy of anthrax toxin to mediate translocation of M . tuberculosis antigens into the cytosol of mammalian cells and may prove useful in delivering proteins and peptides carrying immunodominant mycobacterial antigens into the cytosol.

Br J Neurosurg, 2000 Dec, 14(6), 580 - 2
Bacillus cereus meningitis complicating cerebrospinal fluid fistula repair and spinal drainage; Marshman LA et al.; Non-anthrax Bacillus species are rare, but serious causes of bacterial meningitis in those either immunocompromised or treated with CSF diversion . Although resistant to first-line antibiotics, they usually respond to chloramphenicol . We report a case of fulminant Bacillus cereus meningitis that complicated lumbar spinal drainage which proved resistant to all first-line antibiotics including chloramphenicol.

Saudi Med J, 2001 Jan, 22(1), 6 - 9
Are Saudi Arabian hospitals prepared for the threat of biological weapons?
Memish ZA, Mah MW.
The use of biological weapons has been recorded repeatedly in history . Until recently, biological terrorism had been little discussed or written about . However, events over the past 12 to 18 months have made it clear that likely perpetrators already envisage every possible scenario . Nations and dissident groups exist that have both the motivation and access to utilize biological weapons . In April 1994, a Russian biological weapons expert presented the conclusions of the Russian experts as to the agents most likely to be used: smallpox, anthrax, and plague . Health care workers in the Kingdom of Saudi Arabia (physicians, nurses, and emergency medical technicians) need to be aware of the seriousness of the threat of biological weapons, and to have an approach for the early identification, triage, and management of biological weapons victims . Clues to the occurrence of a bioterrorism attack include the abrupt onset of a large number of cases of a similar disease or syndrome, the occurrence of diseases with unusual geographic or seasonal distribution, and epidemics of non-endemic diseases . Health care workers must maintain a high index of suspicion, involve the hospital epidemiologist or infectious diseases specialist, identify a clear administrative chain-of-command to minimize confusion, and rely on existing networks such as the hospital disaster-and-safety committee to ensure a multidisciplinary response . Maximum readiness can be achieved by periodic readiness drills.

Parassitologia, 2000 Jun, 42(1-2), 173 - 82
The malaria vaccine: seventy years of the great immune hope; Desowitz RS; The cluster of seminal microbiological discoveries at the end of the 19th century through to the first quarter of the 20th century gave rise to the expectation that the control of malaria would be by scientific technology (as opposed to the 'brute force' of bonification/massive engeneering works) and that technology would be immunization by a malaria vaccine . Immunology's foundation was in microbiology and the two related disciplines matured concurrently . Immunization with dead or inactivated microorganisms became immunology's strongest arm, affording protection against many major diseases such as smallpox, anthrax, rabies, yellow fever and tetanus . So why not malaria? In the pre-World War II era there were no chemotherapeutic/prophylactic drugs practical for the control of malaria and a vaccine seemed the easy, rational path to that objective . From 1910 to about 1950 there were numerous attempts in humans and primate and avian models to devise a malaria vaccine . However, it soon became apparent that the malaria parasites, because of their complex, stage-specific antigenic identity as well as their relatively poor immunogenicity, would be much more difficult to use as a vaccine than the bacteria or viruses . There were some experimental successes, but none in humans.

J Bacteriol, 2001 Mar, 183(6), 2111 - 6
Involvement of domain 3 in oligomerization by the protective antigen moiety of anthrax toxin; Mogridge J et al.; Protective antigen (PA), a component of anthrax toxin, binds receptors on mammalian cells and is activated by a cell surface protease . The resulting active fragment, PA(63), forms ring-shaped heptamers, binds the enzymic moieties of the toxin, and translocates them to the cytosol . Of the four crystallographic domains of PA, domain 1 has been implicated in binding the enzymic moieties; domain 2 is involved in membrane insertion and oligomerization; and domain 4 binds receptor . To determine the function of domain 3, we developed a screen that allowed us to isolate random mutations that cause defects in the activity of PA . We identified several mutations in domain 3 that affect monomer-monomer interactions in the PA(63) heptamer, indicating that this may be the primary function of this domain.

Am J Health Syst Pharm, 2001 Feb 1, 58(3), 233 - 7
Citywide pharmaceutical preparation for bioterrorism; Terriff CM et al.; One community's efforts to become pharmaceutically prepared for an attack with biological agents is described . In response to recent bioterrorist activities, including a local scare in 1999 involving anthrax, the pharmacy department at Deaconess Medical Center in Spokane, Washington, was asked to develop a plan for bioterrorism preparedness . A literature search was conducted, and resources, such as the Centers for Disease Control and Prevention, were contacted . For each biological agent, information was compiled about symptom onset, treatment, postexposure prophylaxis, patient isolation precautions, and the availability of antidotes at local hospitals . A procedure was developed for obtaining antidotes that might not be available or stocked in sufficient quantities . After being reviewed by appropriate authorities, the information was presented to area hospitals and trauma centers, drug wholesalers, hospital risk-management personnel, and emergency management personnel . In May 2000 dozens of emergency and medical personnel attended a day-long program on domestic preparedness . Citywide cooperation was obtained on how to respond to a mass exposure to a bioterrorism agent . The job of a pharmacist during a bioterrorism strike is to rapidly disseminate antidotes and information, provide dosage and vaccination schedules for both treatment and prophylaxis, and counsel patients . Medical facilities in Spokane have cooperated to make the community more prepared for a bioterrorist attack.

Rev Sci Tech, 2000 Apr, 19(1), 15 - 22
{Brief review of the history of zoonoses}; Blancou J et al.; By studying the surviving documents describing surveillance and methods of control of zoonoses in the distant past, the history of the fight against these diseases can be retraced . Prior to the 20th Century, the best known zoonoses were, amongst others, rabies, anthrax, glanders, tuberculosis, plague, yellow fever, influenza, and certain zoonotic parasitic diseases . An analysis of historical events yields a number of lessons as to the positive and negative influences of past theories regarding the aetiology, contagiousness and control of these diseases . These lessons serve as a reminder, to all those involved in the fight against emerging zoonoses, of the urgent need for extensive research on the aetiology and mode of transmission of these zoonoses, in addition to the need for timely application of the findings of such research to disease control activities.

Epidemiol Mikrobiol Imunol, 2000 Nov, 49(4), 165 - 73
{Bioterrorism--a public and health threat}; Jezek Z; In recent years the fear of bioterrorism, of secret modernization and dissemination of biological weapons is increasing . Facts detected recently in Iran, Japan and the former Soviet Union provide evidence that there are countries and dissident groups which have access to modern technology of cultivation of dangerous pathogens as well as motivation for their use in acts of terrorism or war . The menace of biological terrorism is nowadays, as compared with the past, much greater . The most feared candidates as regards production of biological weapons are the pathogens of smallpox, anthrax and plague . The author discusses the serious character of possible events associated with terrorist dissemination of these pathogens . It is much esier to produce and use biological weapons than to create effective systems of defence against them . The menace of bioterrorism and bioweapons must not be exaggerated nor underestimated . The possible terrorist use of bioweapons is real . At present even the most advanced industrial countries cannot quarantee effective protection of their populations . Fortunately they are however aware of their present vulnerability . Our society is not equipped to cope with bioterrorism . Preparation and reinforcement of the health services, in particular of sections specialized in the control of infectious diseases is an effective step to divert the sequelae and suffering associated with terrorist use of biological agents . It is essential to be prepared . This calls for time and funds which unfortunately are not plentiful.

Cell Microbiol, 2000 Jun, 2(3), 251 - 8
Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization; Beauregard KE et al.; Immunofluorescence and other methods have been used to probe the self-assembly and internalization of the binary toxin, anthrax lethal toxin (LeTx), in primary murine macrophages . Proteolytic activation of protective antigen (PA; 83 kDa, the B moiety of the toxin) by furin was the rate-limiting step in internalization of LeTx and promoted clearance of PA from the cell surface . A furin-resistant form of PA remained at the cell surface for at least 90 min . Oligomerization of receptor-bound PA63, the 63 kDa active fragment of PA, was manifested by its conversion to a pronase-resistant state, characteristic of the heptameric prepore form in solution . That oligomerization of PA63 triggers toxin internalization is supported by the observation that PA20, the complementary 20 kDa fragment of PA, inhibited clearance of nicked PA . The PA63 prepore, with or without lethal factor (LF), cleared slowly from the cell surface . These studies show that proteolytic cleavage of PA, in addition to permitting oligomerization and LF binding, also promotes internalization of the protein . The relatively long period of activation and internalization of PA at the cell surface may reflect adaptation of this binary toxin that maximizes self-assembly.

J Appl Toxicol, 2001 Jan-Feb, 21(1), 59 - 68
Biological consequences of multiple vaccine and pyridostigmine pretreatment in the guinea pig; Griffiths GD et al.; An investigation of the possible interactions between combinations of vaccines and pyridostigmine bromide (PB) has been undertaken in the guinea pig . This study is part of a research programme funded by the UK Government to determine any effects of the pretreatment regimes given to UK Forces during the Persian Gulf conflict of 1990-1991 . The study was designed to simulate PB administration and to model multiple vaccination protocols that were experienced by UK Forces, modelling a "worst case" situation in which all ten vaccines and PB were administered within a short period of time . Seven of the vaccines were health and hygiene (H+H) vaccines given to protect against endemic diseases and two vaccines to protect against the biological warfare agents anthrax and plague . In addition, pertussis vaccine was administered as an adjuvant to reduce the time to achieve immunity against anthrax . Four groups of eight animals were treated with 1/20th, 1/10th or 1/5th human doses of vaccines or vehicles, respectively . The PB or saline was delivered by implanted 28 day mini-osmotic pumps to achieve a mean red blood cell acetylcholinesterase (AChE) inhibition of around 30% . Body weight, temperature, immunological response, biochemical indices and spontaneous activity were monitored for 72 days . Although immunological responses to bacterial vaccines were observed, there were no remarkable findings in the parameters measured other than minor changes in body weight (4.9% decrease at the 1/5th human dose of vaccines) and temperature increases in response to vaccination . Animals in all groups remained generally healthy and active without visible adverse signs throughout the study . Copyright Crown copyright 2001 . Reproduced with the permission of Her Majesty's Stationery Office . Published by John Wiley & Sons, Ltd.

Biochem Biophys Res Commun, 2001 Feb 16, 281(1), 186 - 92
Trp 346 and Leu 352 residues in protective antigen are required for the expression of anthrax lethal toxin activity; Batra S et al.; The three separate proteins that make up anthrax toxin-protective antigen (PA), edema factor (EF) and lethal factor (LF) act in binary combinations to produce two distinct reactions in experimental animals: edema (PA+EF) and death (PA+LF) . PA is believed to interact with a membrane receptor and, after proteolytic processing, to mediate endocytosis and subsequent translocation of EF or LF into the cytosol . Residues W346, M350, and L352 in loop 3 of domain 2 have been implicated to induce a conformational change when the pH is lowered from 7.4 to 6.5 . Modification of the residues Trp (346), Met (350), and Leu (352) to alanine individually and all the three residues together to alanine residues resulted in the loss of cytotoxic activity in combination with LF . The mutant proteins were able to bind to the cell surface receptor, become cleaved by trypsin, bind LF, and oligomerize . These residues might play an important role in the membrane insertion of PA and/or translocation of LF/EF into the cytosol.

Clin Infect Dis, 2001 Feb 1, 32(3), 446 - 56 Epub 2001 Jan 24.
Risks and prevention of nosocomial transmission of rare zoonotic diseases; Weber DJ et al.; Americans are increasingly exposed to exotic zoonotic diseases through travel, contact with exotic pets, occupational exposure, and leisure pursuits . Appropriate isolation precautions are required to prevent nosocomial transmission of rare zoonotic diseases for which person-to-person transmission has been documented . This minireview provides guidelines for the isolation of patients and management of staff exposed to the following infectious diseases with documented person-to-person transmission: Andes hantavirus disease, anthrax, B virus infection, hemorrhagic fevers (due to Ebola, Marburg, Lassa, Crimean-Congo hemorrhagic fever, Argentine hemorrhagic fever, and Bolivian hemorrhagic fever viruses), monkeypox, plague, Q fever, and rabies . Several of these infections may also be encountered as bioterrorism hazards (i.e., anthrax, hemorrhagic fever viruses, plague, and Q fever) . Adherence to recommended isolation precautions will allow for proper patient care while protecting the health care workers who provide care to patients with known or suspected zoonotic infections capable of nosocomial transmission.

J R Army Med Corps, 2000 Oct, 146(3), 191 - 5
Adverse reactions to anthrax immunisation in a military field hospital; Hayes SC et al.; 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.

J Biol Chem, 2001 Mar 16, 276(11), 8371 - 6 Epub 2000 Dec 11.
Point mutations in anthrax protective antigen that block translocation; Sellman BR et al.; The protective antigen (PA) moiety of anthrax toxin delivers the toxin's enzymatic moieties to the cytosol of mammalian cells by a mechanism associated with its ability to heptamerize and form a transmembrane pore . Here we report that mutations in Lys-397, Asp-425, or Phe-427 ablate killing of CHO-K1 cells by a cytotoxic PA ligand . These mutations blocked PA's ability to mediate pore formation and translocation in cells but had no effect on its receptor binding, proteolytic activation, or ability to oligomerize and bind the toxin's enzymatic moieties . The mutation-sensitive residues lie in the 2beta(7)-2beta(8) and 2beta(10)-2beta(11) loops of domain 2 and are distant both in primary structure and topography from the 2beta(2)-2beta(3) loop, which is believed to participate in formation of a transmembrane beta-barrel . These results suggest that Lys-397, Asp-425, and Phe-427 participate in conformational rearrangements of a heptameric pore precursor that are necessary for pore formation and translocation . Identification of these residues will aid in elucidating the mechanism of translocation and may be useful in developing therapeutic and prophylactic agents against anthrax.

Clin Chem, 2000 Dec, 46(12), 1883 - 93
The role of the clinical laboratory in managing chemical or biological terrorism; Jortani SA et al.; BACKGROUND: Domestic and international acts of terrorism using chemicals and pathogens as weapons have recently attracted much attention because of several hoaxes and real incidents . Clinical laboratories, especially those affiliated with major trauma centers, should be prepared to respond rapidly by providing diagnostic tests for the detection and identification of specific agents, so that specific therapy and victim management can be initiated in a timely manner . As first-line responders, clinical laboratory personnel should become familiar with the various chemical or biological agents and be active participants in their local defense programs . APPROACH: We review the selected agents previously considered or used in chemical and biological warfare, outline their poisonous and pathogenic effects, describe techniques used in their identification, address some of the logistical and technical difficulties in maintaining such tests in clinical laboratories, and comment on some of the analytical issues, such as specimen handling and personal protective equipment . CONTENT: The chemical agents discussed include nerve, blistering, and pulmonary agents and cyanides . Biological agents, including anthrax and smallpox, are also discussed as examples for organisms with potential use in bioterrorism . Available therapies for each agent are outlined to assist clinical laboratory personnel in making intelligent decisions regarding implementation of diagnostic tests as a part of a comprehensive defense program . SUMMARY: As the civilian medical community prepares for biological and chemical terrorist attacks, improvement in the capabilities of clinical laboratories is essential in supporting counterterrorism programs designed to respond to such attacks . Accurate assessment of resources in clinical laboratories is important because it will provide local authorities with an alternative resource for immediate diagnostic analysis . It is, therefore, recommended that clinical laboratories identify their current resources and the extent of support they can provide, and inform the authorities of their state of readiness.

Braz J Infect Dis, 1998 Dec, 2(6), 304 - 307
Facial Cutaneous Anthrax in a Pregnant Woman: a Case Report; Tomasiewicz K et al.; Anthrax remains an uncommon, but worldwide problem, particularly in countries in which domestic animals and processing of animal by-products are an important part of the economy . The disease has received attention recently because of its potential for use in biologic warfare . In Poland during the last 10 years, several human cases of cutaneous anthrax occurred . We report here a case of a pregnant woman with this disease . The lesion was atypical and in a potentially dangerous location since it was on the upper part of the face; a site which could be associated wth either respiratory or central nervous system complications . The patient recovered without complication after antibiotic treatment and local surgery . The fetus and the subsequent labor and delivery were not affected . The case is presented as a reminder of the continued presence of this disease, of the need for attention to its special clinical signs and symptoms, of the need to supervise the agriculture and textile industries, such as by use of vaccines when appropriate, and of the increased concern about this disease in regard to biologic warfare.

Cancer Res, 2000 Nov 1, 60(21), 6061 - 7
Tumor cell-selective cytotoxicity of matrix metalloproteinase-activated anthrax toxin; Liu S et al.; Matrix metalloproteinases (MMPs) are overexpressed in a variety of tumor tissues and cell lines, and their expression is highly correlated to tumor invasion and metastasis . To exploit these characteristics in the design of tumor cell-selective cytotoxins, we constructed two mutated anthrax toxin protective antigen (PA) proteins in which the furin protease cleavage site is replaced by sequences selectively cleaved by MMPs . These MMP-targeted PA proteins were activated rapidly and selectively on the surface of MMP-overexpressing tumor cells . The activated PA proteins caused internalization of a recombinant cytotoxin, FP59, consisting of anthrax toxin lethal factor residues 1-254 fused to the ADP-ribosylation domain of Pseudomonas exotoxin A . The toxicity of the mutated PA proteins for MMP-overexpressing cells was blocked by hydroxamate inhibitors of MMPs, including BB94, and by a tissue inhibitor of matrix metalloproteinases (TIMP-2) . The mutated PA proteins killed MMP-overexpressing tumor cells while sparing nontumorigenic normal cells when these were grown together in a coculture model, indicating that PA activation occurred on the tumor cell surface and not in the supernatant . This method of achieving cell-type specificity is conceptually distinct from, and potentially synergistic with, the more common strategy of retargeting a protein toxin by fusion to a growth factor, cytokine, or antibody.

Biotechniques, 2000 Oct, 29(4), 844 - 8, 850-2, 854 passim
PCR amplification on a microarray of gel-immobilized oligonucleotides: detection of bacterial toxin- and drug-resistant genes and their mutations; Strizhkov BN et al.; PCR amplification on a microarray of gel-immobilized primers (microchip) has been developed . One of a pair of PCR primers was immobilized inside a separate microchip polyacrylamide porous gel pad of 0.1 x 0.1 x 0.02 (or 0.04) micron in size and 0.2 (or 0.4) nL in volume . The amplification was carried out simultaneously both in solution covering the microchip array and inside gel pads . Each gel pad contained the immobilized forward primers, while the fluorescently labeled reverse primers, as well as all components of the amplification reaction, diffused into the gel pads from the solution . To increase the amplification efficiency, the forward primers were also added into the solution . The kinetics of amplification was measured in real time in parallel for all gel pads with a fluorescent microscope equipped with a charge-coupled device (CCD) camera . The accuracy of the amplification was assessed by using the melting curves obtained for the duplexes formed by the labeled amplification product and the gel-immobilized primers during the amplification process; alternatively, the duplexes were produced by hybridization of the extended immobilized primers with labeled oligonucleotide probes . The on-chip amplification was applied to detect the anthrax toxin genes and the plasmid-borne beta-lactamase gene responsible for bacterial ampicillin resistance . The allele-specific type of PCR amplification was used to identify the Shiga toxin gene and discriminate it from the Shiga-like one . The genomic mutations responsible for rifampicin resistance of the Mycobacterium tuberculosis strains were detected by the same type of PCR amplification of the rpoB gene fragment isolated from sputum of tuberculosis patients . The on-chip PCR amplification has been shown to be a rapid, inexpensive and powerful tool to test genes responsible for bacterial toxin production and drug resistance, as well as to reveal point nucleotide mutations.

Vet Hum Toxicol, 2000 Oct, 42(5), 297 - 300
The poison center role in biological and chemical terrorism; Krenzelok EP et al.; Nuclear, biological and chemical (NBC) terrorism countermeasures are a major priority with municipalities, healthcare providers, and the federal government . Significant resources are being invested to enhance civilian domestic preparedness by conducting education at every response level in anticipation of a NBC terroristic incident . The key to a successful response, in addition to education, is integration of efforts as well as thorough communication and understanding the role that each agency would play in an actual or impending NBC incident . In anticipation of a NBC event, a regional counter-terrorism task force was established to identify resources, establish responsibilities and coordinate the response to NBC terrorism . Members of the task force included first responders, hazmat, law enforcement (local, regional, national), government officials, the health department, and the regional poison information center . Response protocols were developed and education was conducted, culminating in all members of the response task force becoming certified NBC instructors . The poison center participated actively in 3 incidents of suspected biologic and chemical terrorism: an alleged anthrax-contaminated letter sent to a women's health clinic; a possible sarin gas release in a high school: and a potential anthrax/ebola contamination incident at an international airport . All incidents were determined hoaxes . The regional response plan establishes the poison information center as a common repository for all cases in a biological or chemical incident . The poison center is one of several critical components of a regional counterterrorism response force . It can conduct active and passive toxicosurveillance and identify sentinel events . To be responsive, the poison center staff must be knowledgeable about biological and chemical agents . The development of basic protocols and a standardized staff education program is essential . The use of the RaPiD-T (R-recognition, P-protection, D-detection, T-triage/treatment) course can provide basic staff education for responding to this important but rare consultation to the poison center.

J Public Health Manag Pract, 2000 Jul, 6(4), 8 - 18
Bioterrorism threats: learning from inappropriate responses; Cole LA; Between April 1997 and June 1999, some 200 mailed or telephoned bioterrorism threats were received at a variety of locations . Usually claiming that anthrax had been released, the threats all proved to be hoaxes . In many instances, local emergency responders treated the more than 13,000 potential victims inappropriately, in particular requiring victims to strip and undergo decontamination with bleach solutions . Narratives of several incidents indicated that many victims were distressed and embarrassed by their treatment . Their experiences underscore the need for improved local response actions and the formulation of a uniform response protocol for public health agencies.

Vaccine, 2000 Sep 15, 19(2-3), 213 - 6
Anthrax vaccine: increasing intervals between the first two doses enhances antibody response in humans; Pittman PR et al.; The influence of dosing interval on the human antibody response to anthrax vaccine adsorbed (AVA) was evaluated in two retrospective serological studies . In both studies, the interval between the first two doses was 2, 3 or 4 weeks . In the first study, banked sera were selected from 89 at-risk individuals at a mean time of 13 days after the second dose of vaccine . In the second study, banked sera were selected from 51 at-risk individuals at a mean time of 48 days following the first dose of AVA . In both studies, the geometric mean anti-protective antigen IgG antibody titer increased significantly as the interval between the two doses increased from 2 to 4 weeks (p=0.0005-0.029) . In the first study, the seroconversion rate also increased as the interval between the first two doses increased (p=0 . 0034) . A prospective, randomized study has been completed and is being analyzed to confirm these findings.

Biotechnol Appl Biochem, 2000 Aug, 32 ( Pt 1), 69 - 72
Anthrax toxin-mediated delivery of cholera toxin-A subunit into the cytosol of mammalian cells; Sharma M et al.; The protective antigen (PA) component of anthrax toxin mediates delivery of either lethal factor (LF) or oedema factor into the cytosol of mammalian cells . The N-terminal domain of LF(1-254) (amino acids 1-254 of LF) binds to PA and, when fused to heterologous proteins, delivers such proteins into the cytosol . In the present study, we fused the catalytic subunit of cholera toxin (CT-A) with LF(1-254) and showed that the fusion protein LF(1-254)-CT-A retains ADP-ribosylation activity in solution and increased intracellular cAMP levels in J774A.1 macrophage cells when added together with PA . A mutant fusion protein, in which arginine-7 of CT-A was replaced with lysine, did not show ADP-ribosylation activity in solution and failed to increase cAMP levels in macrophage cells . The data show that LF(1-254)-CT-A retains its catalytic activity in solution as well as when translocated into the cytosol of eukaryotic cells via an alternative pathway to the GM(1) receptor used by CT.

Acta Trop, 2000 Jul 21, 76(1), 53 - 7
Prevalence and control of zoonotic diseases: collaboration between public health workers and veterinarians in Burkina Faso; Coulibaly ND et al.; Zoonotic diseases constitute a public health problem throughout the world, particularly in the tropics, where their control is restricted by inadequate infrastructure and financial resources . Additionally, there is a lack of information on their significance and distribution . This study, conducted jointly by the Ministries of Health and Animal Resources, aimed to assess the prevalence of zoonotic diseases in Burkina Faso . The data were taken from internal reports of each ministry covering the period January 1-December 31 1996 for the Ministry of Health and for January 1-December 31 1997 for the Ministry of Animal Resources . Zoonotic diseases were divided into viral (rabies, yellow fever, HIV infection/AIDS, and measles), bacterial (tuberculosis, brucellosis, and anthrax) and parasitic (cysticercosis, toxoplasmosis, and leishmaniasis) . For the period under study, the following diseases were reported by the Ministry of Health, tuberculosis, 1314 cases; anthrax, 145 cases; leishmania, 271 cases; rabies, 110 cases; and measles, 46490 cases . The Ministry of Animal Resources reported 69% of rabies cases occurred in dogs; cysticercosis occurred in swine at a prevalence of 0.57%; the prevalence of tuberculosis in cattle, small ruminants and pigs was 0 . 13, 0.013, and 0.029%, respectively; the prevalence of anthrax and echinococcosis was 0.012 and 0.007%, respectively; and finally, the prevalence of bovine brucellosis was 8% in the peri-urban areas . This study revealed that there was a lack of collaboration between the organisational structures and workers in both ministries involved in the control of zoonoses . Links between the two ministries in the field of public health need strengthening.

Acta Trop, 2000 Jul 21, 76(1), 49 - 52
Human behavioural factors implicated in outbreaks of human anthrax in the Tamale municipality of northern Ghana; Opare C et al.; The knowledge, attitude, beliefs and practices of cattle owners, herdsmen, butchers and meat consumers about anthrax were used to provide a better understanding of the major factors responsible for the frequent outbreaks of human anthrax in the Tamale municipality of northern Ghana . A total of 96% of the respondents, made up of 50 cattle owners, 50 herdsmen, 25 butchers and 125 consumers, knew of anthrax and the clinical signs indicative of anthrax in cattle . However, very few knew the causative agent and many attributed the disease to the supernatural . Eight percent of the respondents believed that herbal preparations could protect against human anthrax, while 9% indicated that they would seek help from traditional practitioners or herbalists, if they suspected anthrax . A significant proportion of respondents were of the view that animals, which had died of unknown causes could be eaten because they served as a source of inexpensive meat for the community, especially if the meat was cooked with herbs which was commonly thought to prevent anthrax . These attitudes, taken together with the low income of the population studied, made the consumption of meat from animals, which had died of unknown causes, an attractive option . This increased the vulnerability to human anthrax in an area with frequent anthrax outbreaks in livestock . The results of this study suggest that a public education campaign involving both veterinary and local health personnel on the actual cause and prevention of anthrax could reduce outbreaks of anthrax in people.

Proc Natl Acad Sci U S A, 2000 Jul 5, 97(14), 8027 - 32
Genetically modified anthrax lethal toxin safely delivers whole HIV protein antigens into the cytosol to induce T cell immunity; Lu Y et al.; Bacillus anthrax lethal toxin can be engineered to deliver foreign proteins to the cytosol for antigen presentation to CD8 T cells . Vaccination with modified toxins carrying 8-9 amino acid peptide epitopes induces protective immunity in mice . To evaluate whether large protein antigens can be used with this system, recombinant constructs encoding several HIV antigens up to 500 amino acids were produced . These candidate HIV vaccines are safe in animals and induce CD8 T cells in mice . Constructs encoding gag p24 and nef stimulate gag-specific CD4 proliferation and a secondary cytotoxic T lymphocyte response in HIV-infected donor peripheral blood mononuclear cells in vitro . These results lay the foundation for future clinical vaccine studies.

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