Bioterrorism alleging use of anthrax and interim guidelines for management--United States, 1998.
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From October 30 through December 23, 1998, CDC received reports of a series of bioterroristic threats of anthrax exposure. Letters alleged to contain anthrax were sent to health clinics on October 30, 1998, in Indiana, Kentucky, and Tennessee. During December 17-23 in California, a letter alleged to contain anthrax was sent to a private business, and three telephone threats of anthrax contamination of ventilation systems were made to private and public buildings. All threats were hoaxes and are under investigation by the Federal Bureau of Investigation (FBI) and local law enforcement officials. The public health implications of these threats were investigated to assist in developing national public health guidelines for responding to bioterrorism. This report summarizes the findings of these investigations and provides interim guidance for public health authorities on bioterrorism related to anthrax. (+info)
A randomly amplified polymorphic DNA marker specific for the Bacillus cereus group is diagnostic for Bacillus anthracis.
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Aiming to develop a DNA marker specific for Bacillus anthracis and able to discriminate this species from Bacillus cereus, Bacillus thuringiensis, and Bacillus mycoides, we applied the randomly amplified polymorphic DNA (RAPD) fingerprinting technique to a collection of 101 strains of the genus Bacillus, including 61 strains of the B. cereus group. An 838-bp RAPD marker (SG-850) specific for B. cereus, B. thuringiensis, B. anthracis, and B. mycoides was identified. This fragment included a putative (366-nucleotide) open reading frame highly homologous to the ypuA gene of Bacillus subtilis. The restriction analysis of the SG-850 fragment with AluI distinguished B. anthracis from the other species of the B. cereus group. (+info)
The efforts of WHO and Pugwash to eliminate chemical and biological weapons--a memoir.
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The World Health Organization and the Pugwash Conferences on Science and World Affairs (Nobel Peace Prize 1995) have been involved in questions concerning chemical and biological arms since the early 1950s. This memoir reviews a number of milestones in the efforts of these organizations to achieve the elimination of these weapons through international treaties effectively monitored and enforced for adherence to their provisions. It also highlights a number of outstanding personalities who were involved in the efforts to establish and implement the two major treaties now in effect, the Biological Weapons Convention of 1972 and the Chemical Weapons Convention of 1993. (+info)
Genetic diversity in the protective antigen gene of Bacillus anthracis.
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Bacillus anthracis is a gram-positive spore-forming bacterium that causes the disease anthrax. The anthrax toxin contains three components, including the protective antigen (PA), which binds to eucaryotic cell surface receptors and mediates the transport of toxins into the cell. In this study, the entire 2,294-nucleotide protective antigen gene (pag) was sequenced from 26 of the most diverse B. anthracis strains to identify potential variation in the toxin and to further our understanding of B. anthracis evolution. Five point mutations, three synonymous and two missense, were identified. These differences correspond to six different haploid types, which translate into three different amino acid sequences. The two amino acid changes were shown to be located in an area near a highly antigenic region critical to lethal factor binding. Nested primers were used to amplify and sequence this same region of pag from necropsy samples taken from victims of the 1979 Sverdlovsk incident. This investigation uncovered five different alleles among the strains present in the tissues, including two not seen in the 26-sample survey. One of these two alleles included a novel missense mutation, again located just adjacent to the highly antigenic region. Phylogenetic (cladistic) analysis of the pag corresponded with previous strain grouping based on chromosomal variation, suggesting that plasmid evolution in B. anthracis has occurred with little or no horizontal transfer between the different strains. (+info)
Role of toxin functional domains in anthrax pathogenesis.
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We investigated the role of the functional domains of anthrax toxins during infection. Three proteins produced by Bacillus anthracis, the protective antigen (PA), the lethal factor (LF), and the edema factor (EF), combine in pairs to produce the lethal (PA+LF) and edema (PA+EF) toxins. A genetic strategy was developed to introduce by allelic exchange specific point mutations or in-frame deletions into B. anthracis toxin genes, thereby impairing either LF metalloprotease or EF adenylate cyclase activity or PA functional domains. In vivo effects of toxin mutations were analyzed in an experimental infection of mice. A tight correlation was observed between the properties of anthrax toxins delivered in vivo and their in vitro activities. The synergic effects of the lethal and edema toxins resulted purely from their enzymatic activities, suggesting that in vivo these toxins may act together. The PA-dependent antibody response to LF induced by immunization with live B. anthracis was used to follow the in vivo interaction of LF and PA. We found that the binding of LF to PA in vivo was necessary and sufficient for a strong antibody response against LF, whereas neither LF activity nor binding of lethal toxin complex to the cell surface was required. Mutant PA proteins were cleaved in mice sera. Thus, our data provide evidence that, during anthrax infection, PA may interact with LF before binding to the cell receptor. Immunoprotection studies indicated that the strain producing detoxified LF and EF, isogenic to the current live vaccine Sterne strain, is a safe candidate for use as a vaccine against anthrax. (+info)
Surveillance for adverse events associated with anthrax vaccination--U.S. Department of Defense, 1998-2000.
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Concerns about the potential use of anthrax as a biologic weapon prompted the U.S. Department of Defense (DoD) to announce on December 15, 1997, anthrax vaccination of all U.S. military personnel. This effort is coordinated by the Anthrax Vaccine Immunization Program (AVIP). AVIP plans a phased vaccination process to achieve total force protection against anthrax by 2004. The current phase of implementation includes vaccination of all service members and mission-essential DoD civilian employees assigned or deployed to high-threat areas. On the basis of program monitoring, as of April 12, 2000, 425,976 service members had received 1,620,793 doses of anthrax vaccine adsorbed (AVA) (Bioport, Inc., Lansing, Michigan). Some service members have cited concerns about vaccine safety and efficacy in their decision to refuse vaccination, despite the possibility of administrative or disciplinary actions. To assess anthrax vaccination safety, DoD has conducted surveys of vaccinated personnel. This report describes three completed or ongoing surveys. The findings indicate that rates of local reactions were higher in women than men and that no patterns of unexpected local or systemic adverse events have been identified. (+info)
Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis spore vaccines protect against anthrax.
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Several highly attenuated spore-forming nontoxinogenic and nonencapsulated Bacillus anthracis vaccines differing in levels of expression of recombinant protective antigen (rPA) were constructed. Biochemical analyses (including electrospray mass spectroscopy and N terminus amino acid sequencing) as well as biological and immunological tests demonstrated that the rPA retains the characteristics of native PA. A single immunization of guinea pigs with 5 x 10(7) spores of one of these recombinant strains, MASC-10, expressing high levels of rPA (>/=100 microgram/ml) from a constitutive heterologous promoter induced high titers of neutralizing anti-PA antibodies. This immune response was long lasting (at least 12 months) and provided protection against a lethal challenge of virulent (Vollum) anthrax spores. The recombinant B. anthracis spore vaccine appears to be more efficacious than the vegetative cell vaccine. Furthermore, while results clearly suggest a direct correlation between the level of expression of PA and the potency of the vaccine, they also suggest that some B. anthracis spore-associated antigen(s) may contribute in a significant manner to protective immunity. (+info)
Characterization of the operon encoding the alternative sigma(B) factor from Bacillus anthracis and its role in virulence.
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The operon encoding the general stress transcription factor sigma(B) and two proteins of its regulatory network, RsbV and RsbW, was cloned from the gram-positive bacterium Bacillus anthracis by PCR amplification of chromosomal DNA with degenerate primers, by inverse PCR, and by direct cloning. The gene cluster was very similar to the Bacillus subtilis sigB operon both in the primary sequences of the gene products and in the order of its three genes. However, the deduced products of sequences upstream and downstream from this operon showed no similarity to other proteins encoded by the B. subtilis sigB operon. Therefore, the B. anthracis sigB operon contains three genes rather than eight as in B. subtilis. The B. anthracis operon is preceded by a sigma(B)-like promoter sequence, the expression of which depends on an intact sigma(B) transcription factor in B. subtilis. It is followed by another open reading frame that is also preceded by a promoter sequence similarly dependent on B. subtilis sigma(B). We found that in B. anthracis, both these promoters were induced during the stationary phase and induction required an intact sigB gene. The sigB operon was induced by heat shock. Mutants from which sigB was deleted were constructed in a toxinogenic and a plasmidless strain. These mutants differed from the parental strains in terms of morphology. The toxinogenic sigB mutant strain was also less virulent than the parental strain in the mouse model. B. anthracis sigma(B) may therefore be a minor virulence factor. (+info)