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Protective antigen (PA) is a protein produced by Bacillus anthracis. It forms part of the anthrax toxin and is a key immunogen in US and UK anthrax vaccines. In this study, we have conducted experiments to quantify PA in the supernatants of cultures of B. anthracis Sterne strain, which is the strain used in the manufacture of the UK anthrax vaccine. Then, for the first time, we quantify PA production and degradation via mathematical modelling and Bayesian statistical techniques, making use of this new experimental data as well as two other independent published data sets. We propose a single mathematical model, in terms of delay differential equations (DDEs), which can explain the in vitro dynamics of all three data sets. Since we did not heat activate the B. anthracis spores prior to inoculation, germination occurred much slower in our experiments, allowing us to calibrate two additional parameters with respect to the other data sets. Our model is able to distinguish between natural PA decay and that triggered by bacteria via proteases. There is promising consistency between the different independent data sets for most of the parameter estimates. The quantitative characterisation of B. anthracis PA production and degradation obtained here will contribute towards the ambition to include a realistic description of toxin dynamics, the host immune response, and anti-toxin treatments in future mechanistic models of anthrax infection. [ABSTRACT FROM AUTHOR]

• AVP booster doses elicit significant increases in anti-PA & anti-LF IgG concentrations. • TNA NF 50 response to AVP boosters increases as time interval between doses increases. • JCVI extended interval between AVP booster doses from 1 to 10 years on basis of results. • Anti-PA & anti-LF IgG contribute independently to anthrax lethal toxin neutralisation. We undertook a Phase 4 clinical trial to assess the effect of time interval between booster doses on serological responses to AVP. The primary objective was to evaluate responses to a single booster dose in two groups of healthy adults who had previously received a complete 4-dose primary course. Group A had received doses on schedule while Group B had not had one for ≥2 years. Secondary objectives were to evaluate the safety and tolerability of AVP booster doses, and to gain information on correlates of protection to aid future anthrax vaccine development. Blood samples were taken on Day 1 before dosing, and on Days 8, 15, 29 and 120, to measure Toxin Neutralisation Assay (TNA) NF 50 values and concentrations of IgG antibodies against Protective Antigen (PA), Lethal Factor (LF) and Edema Factor (EF) by ELISA. For each serological parameter, fold changes from baseline following the trial AVP dose were greater in Group B than Group A at every time-point studied. Peak responses correlated positively with time since last AVP dose (highest values being observed after intervals of ≥10 years), and negatively with number of previous doses (highest values occurring in individuals who had received a primary course only). In 2017, having reviewed these results, the Joint Committee on Vaccination and Immunisation (JCVI) updated UK anthrax vaccination guidelines, extending the interval between routine AVP boosters from one to 10 years. Booster doses of AVP induce significant IgG responses against the three anthrax toxin components, particularly PA and LF. Similarly high responses were observed in TNA, a recognised surrogate for anthrax vaccine efficacy. Analysis of the 596 TNA results showed that anti-PA and anti-LF IgG make substantial independent contributions to neutralisation of anthrax lethal toxin. AVP may therefore have advantages over anthrax vaccines that depend on generating immunity to PA alone. [ABSTRACT FROM AUTHOR]

In the years around 1900 one of the most significant practical consequences of new styles of bacteriological thought and practice was the development of preventive vaccines and therapeutic sera. Historical scholarship has highlighted how approaches rooted in the laboratory methods of Robert Koch, Louis Pasteur and their collaborators were transformed in local contexts and applied in diverse ways to enable more effective disease identification, prevention and treatment. Amongst these, the anti-anthrax serum developed by the Italian physician Achille Sclavo (1861–1930) has received little to no attention from historians. This article positions Sclavo's serum as a neglected but significant presence in British microbiology, which achieved widespread uptake amidst a wave of optimism, despite prolonged uncertainty about its mechanism of action and dosage. After being introduced to Britain in 1904 by the enterprising first medical inspector of factories Thomas Morison Legge, within a matter of months the serum became regarded by medical practitioners as an effective treatment of cutaneous anthrax, though access to 'fresh' serum and the necessary speedy diagnosis remained problematic. Like the disease anthrax itself, discussion of 'Sclavo's serum' was out of all proportion to the relatively low number of cases, reflecting a deep-seated fascination with the wider possibilities afforded by effective serum therapy. [ABSTRACT FROM AUTHOR]

Since immemorial time, armed confrontations made use of elements with biological potential for damage, which were already present in nature. The naturally occurring high-risk diseases were skilfully used to bring decisive operational advantages, thus tilting the victory to those who intelligently used the already existing possibilities in the environment. Gradually, with the development of technology and the impact of scientific research, biological factors of high impact on the living force were identified, developed and used in the operational space. The triggers of biological attacks are able to quickly cause serious illness and death of contaminated persons, as well as the decommissioning of targets and land. The action mode is generated by the ability to spread rapidly, achieved by dissemination in air, water or on the ground or by personal contact between individuals. Diseases that can be triggered by using them at critical moments or in carefully selected spaces allow reaching the specific objectives of the aggressor entity. During a turbulent 20th century, deeply involved in a fierce competition for world domination, the great powers noticed the major destructive potential as well as the surprising operational innovations offered by the biological weapon. As a result, they switched to discreet and careful research, followed by testing of the advantages that can be obtained in armed conflicts, through the offensive use of the new weapon into the belligerent area. If, during the First World War, the significant concerns belonged to Germany and Great Britain, during the Second World War, the case of Japan must be given priority. [ABSTRACT FROM AUTHOR]

Comments on B.J. Bernstein's article about the anthrax biological weapon of former Great Britain prime minister Sir Winston Churchill in the 1940s. Claims that Churchill has advocated using anthrax against Germany; Biological warfare; British retaliation against the V-2 bombardment.

Focuses on Great Britain's plans to use biological weapons during World War II. Biological weapons research; Ordering of anthrax bombs from the U.S.; 'Most secret' status of the British biological weapons program; British officials' fears that Germany would learn of British biological warfare agents and stage a retaliatory strike.

The article offers information related to the guidelines from the British HIV Association concerning the utilization of vaccines in adults with HIV positive in 2015. Topics discussed include the aspects of vaccine highlighted in the guidelines, the contraindication of the vaccines in people with severe adverse reaction or allergy, and the availability of the different type of meningococcal vaccine.

Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) occur intermittently and require vigilance and rapid reporting of individual cases. Here, we give a firsthand account of the cases in London during an outbreak of heroin-associated anthrax during 2009-2010 in the United Kingdom. This new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. During 2012-13, additional cases of heroin-associated anthrax among PWIDs in England and other European countries were reported, suggesting that anthrax-contaminated heroin remains in circulation. Antibacterial drugs used for serious soft tissue infection are effective against anthrax, which may lead to substantial underrecognition of this novel illness. The outbreak in London provides a strong case for ongoing vigilance and the use of serologic testing in diagnosis and serologic surveillance schemes to determine and monitor the prevalence of anthrax exposure in the PWID community. [ABSTRACT FROM AUTHOR]

Many accounts of Australian economic and social development have centred on the importance of pastoralism. However, whilst these have acknowledged the critical role played by trade between Britain and Australia in fleeces and wool-based manufactured goods, the roles and importance of anthrax have remained hidden. This article maps the exchange of intellectual and practical tools designed to combat human and animal anthrax between Britain and Australia in the late--nineteenth and early--twentieth centuries. In this period there was a dynamic, two-way exchange of theories and practices between Britain and Australia, facilitated by lay and professional investigations and a proactive periodical press. French bacteriologists also played a prominent role, exporting Pasteurian vaccination methods to Australia. These exchanges had a significant impact on attempts to control anthrax in at-risk districts and populations. By analysing anthrax in this fashion, we see that international communication networks aided the spread of intellectual and practical tools of disease prevention. [ABSTRACT FROM AUTHOR]

Historians have largely moved away from any simple notion of a late-nineteenth century bacteriological revolution. Increasingly they characterise the ways in which older, sanitarian, public-health approaches and newer, laboratory-based, germ-theoretic approaches to disease co-existed. A re-examination of the public life of industrial anthrax in Britain in the decades around 1900 reveals the persistence of a number of sanitarian themes. Bradford—the centre of the world's wool industry—was the testing ground for early regulation designed to combat the disease. Factory inspectors and other public officials, many unfamiliar with the biology of anthrax, assimilated local efforts to remove dirt and dust from industry into national legislation, largely ignoring the presence of the causative organism, Bacillus anthracis, and its highly resilient spores. Anthrax, it is argued here, had an important social role: beyond the confines of the laboratory, it was at the centre of a continuing sanitary approach to disease prevention. [ABSTRACT FROM PUBLISHER]

The recent anthrax outbreak among injecting drug users (IDUs) in Europe has highlighted an ongoing problem with severe illness resulting from spore-forming bacteria in IDUs. We collated the numbers of cases of 4 bacterial illnesses (botulism, tetanus, Clostridium novyi, and anthrax) in European IDUs for 2000 to 2009 and calculated population rates. Six countries reported 367 cases; rates varied from 0.03 to 7.54 per million people. Most cases (92%) were reported from 3 neighboring countries: Ireland, Norway, and the United Kingdom. This geographic variation needs investigation. [ABSTRACT FROM AUTHOR]

Background: Incursions of contagious diseases of livestock into disease-free zones are inevitable as long as the diseases persist elsewhere in the world. Knowledge of where, when and how incursions have occurred helps assess the risks, and regionalize preventative and reactive measures. Methodology: Based on reports of British governmental veterinary services, we review occurrence of the former OIE List A diseases, and of Aujeszky's disease, anthrax and bovine tuberculosis (bTB) in farm-animals in Great Britain (GB) between 1938 and 2007. We estimate incidence of each disease on GB agricultural holdings and fraction of susceptible farm-animals culled to control the disease each year. We then consider the frequency and incidence of the diseases in Scotland alone. The limitations of available data on historical disease occurrence and denominator populations are detailed in Text S2. Conclusions: The numbers of livestock and poultry farmed in GB grew over the years 1938-2007; the number of agricultural holdings decreased. An amalgamation of production on larger holdings took place from the 1940s to the 1980s. The maximum annual incidence of a reviewed disease in GB 1938-2007 was reported for bTB, 1.69% of holdings in 1961. This was followed by Newcastle disease, 1.50% of holdings in 1971, and classical swine fever, 1.09% of holdings in 1940. The largest fractional cull of susceptible livestock in a single year in each of the four decades 1950s-1980s was due to a viral disease primarily affecting swine. During the periods 1938-1949 and 2000-2007 this was due to outbreaks of foot and mouth disease. In the absence of incursions of the former OIE List A diseases in the 1990s, this was due to bTB. Over the 70 years, the diseases were reported with lower frequency and lower annual incidence in Scotland, as compared to when these statistics are considered for GB as a whole. [ABSTRACT FROM AUTHOR]

Aim: To analyse the growth of Bacillus anthracis during simulations of the UK anthrax vaccine manufacturing process. Methods and Results: Simulated vaccine production runs were performed using the toxigenic, acapsulate Sterne 34F2 strain of B. anthracis in semi-defined medium. After rising during the logarithmic growth phase, the pH of the culture starts to fall at about 18 h from pH 8·7 to reach <7·6 at 26 h, coincident with consumption of glucose and optimal production of protective antigen (PA; 7·89 g ml−1, SD 1·0) and lethal factor (LF; 1·85 g ml−1, SD 0·29). No increased breakdown of toxin antigens was seen over the 26–32 h period. When glucose was exhausted, amino acids (principally serine) were utilized as an alternative carbon source. Sporulation was not observed during the 32 h. Conclusions: PA and LF, the principal constituents in the UK anthrax vaccine, undergo little degradation during vaccine fermentation. The vaccine manufacturing process is robust and reproducible. Significance and Impact of the Study: This is the first detailed analysis of the manufacturing process used for the UK acellular anthrax vaccine; insight gained into the process will support continued and safe vaccine manufacture. [ABSTRACT FROM AUTHOR]

This article describes UK and US responses to 9/11 and the subsequent anthrax attacks, referring to ‘biodefence’ and the civilian structures of disaster preparedness. Following a review of initiatives undertaken in each country the article details principal differences between the two systems, the federal nature of the US response and the more localised arrangements preferred in the UK. Finally, with reference to certain international standards articulated by the World Health Organisation, the article concludes with some critical reflections on recent policy developments. International standards promote the civilian character of preparedness programmes and their connections to public health infrastructure. This is being challenged by US developments that emphasise the role of the military while, in the UK, there remain questions about the capacity of civilian structures. [ABSTRACT FROM AUTHOR]

The decades-long contamination of Gruinard Island by anthrax is now a well-known part of the history of biological weapons (BW) development, as well as that of military encroachments in the Scottish Highlands and Islands (and the authorities' rather less persistent efforts at damage limitation). Some accounts have included the related episode, reportedly well-remembered by local people, of anthrax contamination on the mainland close to Gruinard. This occurred in 1942-43, when BW experiments were conducted on the island as part of the war effort by scientists from Porton Down under the auspices of the British government. After much top-level discussion, payments were made to the owners of animals that had died as a result of the contamination. The episode had a bearing on discussions about the future of the island and on subsequent policy with regard to the siting, conduct and secrecy of BW experiments. [ABSTRACT FROM AUTHOR]

The article presents an update on the British Health Protection sector from October 2001 to December 2001. Among the activities done by health protection workers during the period was examining the impact of harmful microorganisms such as anthrax and the rising number of cases related to sexually transmitted diseases such as HIV infection. The British Department of Health also responded to the problem since it launched its first National Strategy for Sexual Health and HIV on July 27, 2001.

The article explores the influences behind the changes in the policies of the key departments responsible for the investigation and prevention of anthrax infection in the wool textiles industries in Great Britain from 1880-1939. The author claims that one important episode in the evolution of occupational health measures in Great Britain was the development of government policies for the regulation of anthrax and their impact on the wool textiles industry. It is noted that the prohibition of designated imports, unless first treated by a disinfecting station, was provided by the Anthrax Prevention Act of 1919.

Background and objective:Cutaneous anthrax usually has a mortality rate of less than 1 per cent. However, since December 2009 there have been more than 13 deaths in the UK due to anthrax-contaminated heroin. We therefore wish to raise clinical awareness of this treatable disease.Case report:We describe the case of a heroin user with an equivocal presentation of cellulitis in the neck. Within 36 hours, this led to death due to cutaneous anthrax.Conclusion:Whilst cutaneous anthrax remains rare, this case report aims to raise awareness of the fact that the symptoms and signs of this condition in intravenous drug users may not always fit the typical picture. [ABSTRACT FROM PUBLISHER]

The manufacture of the UK Anthrax vaccine (AVP) focuses on the production of Protective Antigen (PA) from the Bacillus anthracis Sterne strain. Although used for decades, several of AVP's fundamental properties are poorly understood, including its exact composition, the extent to which proteins other than PA may contribute to protection, and whether the degree of protection varies between individuals.This study involved three innovative investigations. Firstly, the composition of AVP was analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS), requiring the development of a novel desorption method for releasing B. anthracis proteins from the vaccine's aluminum-containing adjuvant. Secondly, computational MHC-binding predictions using NetMHCIIpan were made for the eight most abundant proteins of AVP, for the commonest HLA alleles in multiple ethnic groups, and for multiple B. anthracis strains. Thirdly, antibody levels and toxin neutralizing antibody (TNA) levels were measured in sera from AVP human vaccinees for both PA and Lethal Factor (LF).It was demonstrated that AVP is composed of at least 138 B. anthracis proteins, including PA (65%), LF (8%) and Edema Factor (EF) (3%), using LC-MS/MS. NetMHCIIpan predicted that peptides from all eight abundant proteins are likely to be presented to T cells, a pre-requisite for protection; however, the number of such peptides varied considerably between different HLA alleles.These analyses highlight two important properties of the AVP vaccine that have not been established previously. Firstly, the effectiveness of AVP within humans may not depend on PA alone; there is compelling evidence to suggest that LF has a protective role, with computational predictions suggesting that additional proteins may be important for individuals with specific HLA allele combinations. Secondly, in spite of differences in the sequences of key antigenic proteins from different B. anthracis strains, these are unlikely to affect the cross-strain protection afforded by AVP.

We report the draft genome sequence of Bacillus anthracis UR-1, isolated from a fatal case of injectional anthrax in a German heroin user. Analysis of the genome sequence of strain UR-1 may aid in describing phylogenetic relationships between virulent heroin-associated isolates of B. anthracis isolated in the United Kingdom, Germany, and other European countries. [ABSTRACT FROM AUTHOR]

This section offers news briefs related to health in Great Britain. The Health protection Agency reported that an injecting heroin user has tested positive for anthrax and is undergoing treatment in a hospital in London. A study presented to the annual Society for Endocrinology meeting in 2010 suggests the need to increase the provision of medical and social support for patients with chronic diseases to return to work. The Scottish government has launched a campaign to urge people at risk of having the hepatitis C virus to undergo testing.

The article presents developments related to veterinary medicine. It was reported that anthrax has been well recognized in livestock and humans in Zimbabwe and outbreaks have been reported in the surrounding countries. According to another report, distension of the gallbladder can arise as a result of an obstruction or because of anorexia. Another report cites that Mycoplasma bovis is not a common cause of mastitis in herds in Great Britain.

Reports that the United Kingdom Health Laboratory Service has released provisional guidelines on how to deal with a deliberate release of anthrax in the United Kingdom, following the outbreaks in the United States. Information in the guidelines, including how to recognize various forms of the infection; Need for emergency workers to wear protective equipment; Recommended treatment with ciprofloxacin.

Presents news briefs related to medicine and health as of July 29, 2000. Details of a lawsuit filed by Planned Parenthood against Bartell Drug Company, which fails to provide its female employees insurance coverage for contraception; Efforts of British medical authorities to reduce the use of general anesthesia in dentistry; Details of an outbreak of anthrax in Romania; Others.

Explores the possible cause of deaths among heroin users in Great Britain. Description of how the victims die; Information on anthrax, a biological warfare agent; Details concerning Clostridia.

Examines a fatal case of pulmonary anthrax in Great Britain. Diagnosis of the disease; Occurrence of abdominal pain and dyspnea as the main symptoms; Management and treatment of the disease.