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Anthrax
Published in Meera Chand, John Holton, Case Studies in Infection Control, 2018
Inhalational anthrax results from the inhalation of B. anthracis spores, which may occur while working with contaminated animal products such as wool, hides, or bone meal. Inhalational anthrax also has occurred from deliberate and accidental release of weaponized spore preparations. Spores are phagocytosed by alveolar macrophages and transported to mediastinal lymph nodes where they germinate, multiply, and release toxins causing haemorrhagic necrosis. The incubation period for inhalation anthrax is estimated to be 1 to 7 days, although it may be significantly longer. Early symptoms are entirely nonspecific but experience from the 2001 bioterrorism outbreak in the US (where exposed individuals were identified early) shows that early disease may respond to antibiotics. Without treatment, the prodromal phase is followed by a fulminant bacteraemic phase with an almost universally fatal outcome.
Clarithromycin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Clarithromycin has in vitro activity against B. anthracis. It is one of the secondary antimicrobials that could be added to doxycycline or ciprofloxacin in the treatment of inhalational anthrax (Brook, 2002).
Potential Bioterrorism Concerns
Published in Joseph R. Masci, Elizabeth Bass, Ebola, 2017
Joseph R. Masci, Elizabeth Bass
If used in a biological attack, Ebola virus would require direct person-to-person physical contact, unlike smallpox, plague, or anthrax. Both smallpox and inhalational anthrax are transmitted primarily through the respiratory tract by aerosol droplets. Plague, in its inhalational form, is transmitted in a similar fashion and is also transmissible by the bite of an infected flea. Both smallpox and plague carry the risk of person-to-person transmission. Transmission by the respiratory tract has not been documented with Ebola virus. Nonetheless, even limited to direct person-to-person transmission, Ebola virus would pose the risk of great lethality, and challenges in providing medical resources to treat large numbers of patients while protecting health care workers from infection. Any of these putative agents of bioterrorism, if released, would cause great public anxiety and likely panic, with the attendant overwhelming demand placed on health care services and emergency response systems.
Vaccines against anthrax based on recombinant protective antigen: problems and solutions
Published in Expert Review of Vaccines, 2019
Olga A. Kondakova, Nikolai A. Nikitin, Ekaterina A. Evtushenko, Ekaterina M. Ryabchevskaya, Joseph G. Atabekov, Olga V. Karpova
Therefore, subunit rPA-based vaccines were revealed to have good safety and immunogenicity profile in clinical studies and are capable to confer protection in animal models of inhalational anthrax. Clinical trials are being conducted on several full-size rPA-based vaccines obtained in various expression systems (B. anthracis, E. coli, B. brevis, P. fluorescens), including both wild-type PA and mutant forms resistant to proteolysis. Chimeric vaccines based on PA and other B. anthracis antigens (LF, PDGA, BclA) are also forward-looking for the following development, however stability of such vaccines should be explored to assess their potential.
Anthrax prevention through vaccine and post-exposure therapy
Published in Expert Opinion on Biological Therapy, 2020
Manish Manish, Shashikala Verma, Divya Kandari, Parul Kulshreshtha, Samer Singh, Rakesh Bhatnagar
Anthrax is primarily a disease of herbivore mammals that occasionally infect other carnivores or omnivores including humans. Although anthrax is endemic to parts of Africa, Asia, the Americas, and Europe where it is frequently reported in the wild, the incidences of naturally acquired anthrax in humans are rare [1,2]. The etiological agent of anthrax is primarily the Gram-positive spore-forming bacterium Bacillus anthracis carrying the virulence plasmids pXO1 and pXO2, but at rare instances, it also occurs as a result of infection with other similar plasmid carrying B. cereus group isolates, e.g., B. cereus and B. thuringiensis [3–5]. Depending on the site of infection and clinical manifestations, anthrax can be cutaneous, gastrointestinal, inhalational, and injectional [5]. Injectional anthrax resulting from the use of contaminated heroin has been reported prominently since 2009. Cutaneous anthrax is the most commonly observed form mainly reported as an occupational disease in people handling animals and animal products while gastrointestinal anthrax is commonly reported from people eating wild kills [1,6]. Inhalational anthrax, though quite rare, is the most fatal form that is primarily associated with the intentional aerial release or the secondary aerosolization of B. anthracis spores. For example, in the well documented postal bioterror attack of the USA in the year 2001 where individuals contracted inhalational anthrax as a result of inhaling the spores aerosolized on the opening of the spores laden envelops, 5 out of 11 patients contracting the disease died despite the best supportive care and aggressive multidrug antibiotic treatment provided [7]. Similarly, in injectional anthrax, the high mortality rate has been observed in the documented cases, i.e., 26 deaths out of 70 confirmed cases [8].
Efficacy assessment of a triple anthrax chimeric antigen as a vaccine candidate in guinea pigs: challenge test with Bacillus anthracis 17 JB strain spores
Published in Immunopharmacology and Immunotoxicology, 2021
Masoud Abdous, Sadegh Hasannia, Ali Hatef Salmanian, Seyed-Shahryar Arab
Anthrax is an acute infection in humans and animals caused by B. anthracis. There are commercial anthrax vaccines consisting of Bacillus anthracis spore and protective antigen (PA) to prevent veterinary and human infection, respectively. Veterinary anthrax vaccine has many limitations. First, sick, weak, and young (under three months of age) cattle should not be vaccinated; second, the cattle should be slaughtered at least 3 weeks after vaccination (6 weeks for pregnant animals) and third, there is a possibility of anaphylactic reactions after vaccination of some sensitive livestock breeds requiring veterinary care and adrenaline injection [18]. Furthermore, the FDA approved human anthrax vaccine has a 92.5% efficacy for protection in both cutaneous and inhalational anthrax cases and may not protect all individuals [22]. Therefore, improved methods should be used in order to reduce or eliminate common problems of veterinary and human anthrax vaccines. Many studies found that fusion of different domains of anthrax antigens could be considered a more efficient potential candidate subunit vaccine compared to single antigen vaccines, and also showed the functional role of antibodies in protection against microbial infections [23,24]. Some studies showed that not only the protective antigen (PA) could play an important role in protection against anthrax but also the lethal factor (LF) and the edema factor (EF) stimulate the production of toxin neutralizing antibodies. In addition, PA with LF/EF separately or in the fusion form has synergistic effects as a potential subunit vaccine. It has been reported that a combination of antibodies against PA and LF increases the efficiency of the anthrax toxins neutralization capacity, offers 100% protection against B. anthracis challenges in immunized mice models, and has synergistic protective efficacy [4,25]. Moreover, EF plays a role in eliciting protective immunity against anthrax and should be included in the new generation of multi-component subunit vaccines [26]. EF neutralizing antibodies may cross-react with LF and further protect host cells from anthrax toxins because of the structural similarities between the first domains of EF (EFD1) and the first domains of LF (LFD1) [26]. Furthermore, neutralization of EF and PA could produce synergistic beneficial effects [27]. Previous studies found that chimeric protein produced by fuzing the protective antigen (PA)-binding domain of lethal factor (LFn) to dominant-negative inhibitory PA (DPA) called LFn-DPA. LFn-DPA exhibits a strong potency in rescuing mice from challenge with LeTx. Anti-LF monoclonal antibodies also could cross-react with EF [28,29]. Other study showed that a chimeric vaccine comprising LFD1 and the C-terminal domain of PA (PAD4) would offer a broader spectrum of protection compared to PA alone [4]. Another study displayed that the use of PA-LFD1 chimeric protein enhanced the humoral and cellular immune response in mice, and concluded that this protein could be a better alternative to the PA-based recombinant anthrax vaccine [12].