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Sample records for anthrax vaccines

  1. Anthrax Vaccine

    Science.gov (United States)

    What is anthrax?Anthrax is a serious disease that can affect both animals and humans. It is caused by bacteria called Bacillus anthracis. People can get anthrax from contact with infected animals, wool, meat, or ...

  2. Anthrax vaccine associated deaths in miniature horses.

    Science.gov (United States)

    Wobeser, Bruce K

    2015-04-01

    During a widespread anthrax outbreak in Canada, miniature horses were vaccinated using a live spore anthrax vaccine. Several of these horses died from an apparent immune-mediated vasculitis temporally associated with this vaccination. During the course of the outbreak, other miniature horses from different regions with a similar vaccination history, clinical signs, and necropsy findings were found.

  3. Anthrax Vaccines: Pasteur to the Present

    Science.gov (United States)

    2006-01-01

    muco- sal immunity would result in superior protection [83, 84]. Strategies to elicit mucosal immunity to anthrax include oral vaccination with...Tafaro, A., Fischer, R., Leppla, S. H., Fujihashi, K. and McGhee, J. R. (2003) Effective mucosal immunity to anthrax: neutralizing antibodies and

  4. 9 CFR 113.66 - Anthrax Spore Vaccine-Nonencapsulated.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Anthrax Spore Vaccine-Nonencapsulated. 113.66 Section 113.66 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS Live Bacterial Vaccines § 113.66 Anthrax Spore Vaccine—Nonencapsulated. Anthrax Spore...

  5. Anthrax Vaccine as a Component of the Strategic National Stockpile: A Dilemma for Homeland Security

    Science.gov (United States)

    2009-12-01

    as a prophylaxis for anthrax infection. Instead, the CDC encourages the use of antibiotics, such as penicillin , ciprofloxacin, and doxycycline, as...discovered “ hypersensitivity pneumonitis following anthrax vaccination,” warning physicians to be attentive to “vaccine related complications” (Timmer...anthrax vaccine as a possible cause of hypersensitivity pneumonitis after anthrax vaccination (Oransky, 2003, p. 543). In summary, while some literature

  6. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines.

    Science.gov (United States)

    Laws, Thomas R; Kuchuloria, Tinatin; Chitadze, Nazibriola; Little, Stephen F; Webster, Wendy M; Debes, Amanda K; Saginadze, Salome; Tsertsvadze, Nikoloz; Chubinidze, Mariam; Rivard, Robert G; Tsanava, Shota; Dyson, Edward H; Simpson, Andrew J H; Hepburn, Matthew J; Trapaidze, Nino

    2016-01-01

    Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens.

  7. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines.

    Directory of Open Access Journals (Sweden)

    Thomas R Laws

    Full Text Available Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees or anti-LF (in AVP vaccinees antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens.

  8. Appropriation and commercialization of the Pasteur anthrax vaccine.

    Science.gov (United States)

    Cassier, Maurice

    2005-12-01

    Whereas Pasteur patented the biotechnological processes that he invented between 1857 and 1873 in the agro-food domain, he did not file any patents on the artificial vaccine preparation processes that he subsequently developed. This absence of patents can probably be explained by the 1844 patent law in France that established the non-patentable status of pharmaceutical preparations and remedies, including those for use in veterinary medicine. Despite the absence of patents, the commercial exploitation of the anthrax vaccine in the 1880s and 1890s led to a technical and commercial monopoly by Pasteur's laboratory as well as the founding of a commercial company to diffuse the vaccine abroad. Pasteur repeatedly refused to transfer his know-how and anthrax vaccine production methods to foreign laboratories, on the grounds that he wished to control the quality of the vaccines produced. Indeed, it was relatively difficult to transfer a method that was not yet perfectly stabilized in the early 1880s. Pasteur also wanted to maintain the monopoly of his commercial company and to increase the profits from vaccine sales so that the Institut Pasteur could be financially independent. The 'Pasteur anthrax vaccine' operating licences are described and analysed in detail in this article.

  9. 76 FR 34994 - Vaccine To Protect Children From Anthrax-Public Engagement Workshop

    Science.gov (United States)

    2011-06-15

    ... HUMAN SERVICES Vaccine To Protect Children From Anthrax--Public Engagement Workshop AGENCY: Office of... workshop on July 7, 2011, to discuss vaccine to protect children from anthrax. This meeting is open to the... vaccine to protect children would be to use an investigational new drug (IND) clinical protocol....

  10. Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

    Science.gov (United States)

    Mangal, Sharad; Pawar, Dilip; Agrawal, Udita; Jain, Arvind K; Vyas, Suresh P

    2014-02-01

    The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

  11. Deletion modification enhances anthrax specific immunity and protective efficacy of a hepatitis B core particle-based anthrax epitope vaccine.

    Science.gov (United States)

    Yin, Ying; Zhang, Sheng; Cai, Chenguang; Zhang, Jun; Dong, Dayong; Guo, Qiang; Fu, Ling; Xu, Junjie; Chen, Wei

    2014-02-01

    Protective antigen (PA) is one of the major virulence factors of anthrax and is also the major constituent of the current anthrax vaccine. Previously, we found that the 2β2-2β3 loop of PA contains a dominant neutralizing epitope, the SFFD. We successfully inserted the 2β2-2β3 loop of PA into the major immunodominant region (MIR) of hepatitis B virus core (HBc) protein. The resulting fusion protein, termed HBc-N144-PA-loop2 (HBcL2), can effectively produce anthrax specific protective antibodies in an animal model. However, the protective immunity caused by HBcL2 could still be improved. In this research, we removed amino acids 79-81 from the HBc MIR of the HBcL2. This region was previously reported to be the major B cell epitope of HBc, and in keeping with this finding, we observed that the short deletion in the MIR not only diminished the intrinsic immunogenicity of HBc but also stimulated a higher titer of anthrax specific immunity. Most importantly, this deletion led to the full protection of the immunized mice against a lethal dose anthrax toxin challenge. We supposed that the conformational changes which occurred after the short deletion and foreign insertion in the MIR of HBc were the most likely reasons for the improvement in the immunogenicity of the HBc-based anthrax epitope vaccine.

  12. Military hospitalizations among deployed US service members following anthrax vaccination, 1998-2001.

    Science.gov (United States)

    Wells, Timothy Steven; Sato, Paul A; Smith, Tyler Clain; Wang, Linda Zhenling; Reed, Robert John; Ryan, Margaret Angela Kappel

    2006-01-01

    Safety concerns have confronted the Department of Defense Anthrax Vaccine Immunization Program since inception in 1998. To determine if anthrax vaccination was associated with an increased risk of hospitalization, a historical cohort study utilizing pre- and post-anthrax-vaccination hospitalizations was undertaken and analyzed with Cox proportional hazards models. The study population consisted of 170,723 active duty US service members who were anthrax-vaccinated and deployed during the time period January 1, 1998 to December 31, 2001. Study outcomes included hospitalizations due to any-cause, 14 broad International Classification of Diseases diagnostic categories, autoimmune organ specific and organ non-specific hospitalizations, and asthma. After adjustment, anthrax vaccination was associated with significantly fewer hospitalizations for any-cause, diseases of the blood and blood forming organs, and diseases of the respiratory system. Comparing anthrax post-vaccination hospitalization experience with the pre-vaccination period resulted in no significant increased hazard for any of the hospitalization outcomes studied. Although there was no apparent increase in risk of morbidity in this study population, the relationship between anthrax vaccine and deployment on health outcomes among US service members needs further study.

  13. Enhancement of the Anthrax AVA Vaccine with CpG ODN’s

    Science.gov (United States)

    2005-08-28

    NUMBER OF PAGES 20. LIMITATION OF ABSTRACT UL - 28-Aug-2005 Final Report on ACCELERATE ANTHRAX: CpG 7909 Vaccine Adjuvant Program Report Title...Vaccine Adsorbed (BioThrax?) Combined with CPG 7909 in Normal Volunteers” was completed and presented at the 2005 Interscience Conference on Antimicrobial...Agents and Chemotherapy in a poster entitled “Marked Enhancement Of Antibody Response To Anthrax Vaccine Adsorbed With CPG 7909 In Healthy

  14. Anthrax, Toxins and Vaccines: A 125-Year Journey Targeting Bacillus anthracis

    Science.gov (United States)

    2009-01-01

    after their inception. Since these early begin- nings, additional medical history linked to B. anthracis coincides in many ways with vac- cines that...by vaccination. Hopefully, the reader will be challenged to think of how existing anthrax vaccines, especially those meant for humans, can be...improved with available knowledge/technology. The many current anthrax vaccines are linked to Louis Pasteur’s seminal experiments at Pouilly Ie-Fort in

  15. Protective-antigen (PA) based anthrax vaccines confer protection against inhalation anthrax by precluding the establishment of a systemic infection.

    Science.gov (United States)

    Merkel, Tod J; Perera, Pin-Yu; Lee, Gloria M; Verma, Anita; Hiroi, Toyoko; Yokote, Hiroyuki; Waldmann, Thomas A; Perera, Liyanage P

    2013-09-01

    An intense effort has been launched to develop improved anthrax vaccines that confer rapid, long lasting protection preferably with an extended stability profile amenable for stockpiling. Protective antigen (PA)-based vaccines are most favored as immune responses directed against PA are singularly protective, although the actual protective mechanism remains to be unraveled. Herein we show that contrary to the prevailing view, an efficacious PA-based vaccine confers protection against inhalation anthrax by preventing the establishment of a toxin-releasing systemic infection. Equally importantly, antibodies measured by the in vitro lethal toxin neutralization activity assay (TNA) that is considered as a reliable correlate of protection, especially for PA protein-based vaccines adjuvanted with aluminum salts appear to be not absolutely essential for this protective immune response.

  16. Effect of Aluminum Hydroxide Adjuvant and Formaldehyde in the Formulation of rPA Anthrax Vaccine

    Science.gov (United States)

    2007-01-02

    dose, the recom- ended maximum concentration for anthrax vaccines based pon rPA is 500 g per dose. Our first experiment exam- ned the serological...anthrax. Infect Immun 2006;74:1016–24. 48] Herrmann JE, Wang S, Zhang C, Panchal RG, Bavari S, Lyons CR, et al. Passive immunotherapy of Bacillus anthracis

  17. [Vaccines against anthrax in animals, from Louis Pasteur to our day].

    Science.gov (United States)

    Shlyakhov, E; Blancou, J; Rubinstein, E

    1996-09-01

    The authors outline the history of vaccination against anthrax in animals, from the end of the 19th century to the present time. The three main steps in the production of specific vaccines are described in detail: production of vaccines from live, encapsulated bacteria, followed by vaccines from live, unencapsulated bacteria and, finally, subunit vaccines. Advantages and disadvantages of these three types of vaccine, some of which are still in use today, are described and discussed.

  18. Immunological dynamics in response to two anthrax vaccines in mice

    Institute of Scientific and Technical Information of China (English)

    L(U) Jin; HE Rui; DONG Mei; ZHANG LiangYan; WANG XiLiang

    2008-01-01

    In order to understand the variation of humoral and cellular immune responses to A16R live spore and AVA vaccine and to identify efficient immunological parameters for the early evaluation of post immu-nization in mice, we dynamically monitored the antibody production and cellular responses after the vaccination of Balb/C mice with the anthrax vaccines. The results show that both anti-AVA and anti-Spore antibodies were detectable in the A16R live spore vaccinated group while high titers of anti-AVA antibodies but not anti-Spore antibodies existed in the AVA-immunized group, IgG1 and IgG2 were the major subtypes of IgG in both of the two groups. However, the IgG2a level was significantly higher in the A16R group than in the AVA group. At the cellular level, responses of antigen-specific TH2, TH1 and plasma cells were detected. The peripheral TH2 responses could be seen on day 5 after vac-cination, and remained at a high level throughout the experiment (from day 5 post primary immuniza-tion to day 60 post the tertiary immunization); the TH1 responses to A16R vaccine appeared on day 5, while the responses to AVA could only be detected by day 7 after the secondary immunization; a low level of TH1 responses could be observed at the end of the experiment. Antigen-specific plasma cells could be found in the peripheral blood of both the immunized groups, however, the responses in the A16R group appeared earlier, lasted longer, and shown an ascending tendency until the end of the ex-periment when the plasma cell responses in the AVA group were reduced to a very low level. The re-sults suggest that the multiple antigen containing A16R live spore vaccine induces better immune re-sponses than AVA. Combined with serum antibody titers, TH2, TH1 and plasma cell responses could be used as immunological parameters for the evaluation of vaccine efficacy, These findings may afford new insight into the early evaluation of vaccination as well as being a powerful strategy for vaccine

  19. Anthrax

    Science.gov (United States)

    2009-01-01

    antigen (P A) using immunoglobulin G (lgG) antibodies in response to the bioterrorist anthrax plot in 2001. ELISA proved extremely useful in the...essential for binding to P A. Fusion of this highly conserved N-terminal sequence to other toxins, such as Shiga and diphtheria , can cause toxic...assay, blood cultures, motility tests, enzyme-linked immunosorbent assays ( ELISA ), and fluorescent covalent microsphere immunoassay (FCMIA

  20. Immunological dynamics in response to two anthrax vaccines in mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In order to understand the variation of humoral and cellular immune responses to A16R live spore and AVA vaccine and to identify efficient immunological parameters for the early evaluation of post immu- nization in mice, we dynamically monitored the antibody production and cellular responses after the vaccination of Balb/C mice with the anthrax vaccines. The results show that both anti-AVA and anti-Spore antibodies were detectable in the A16R live spore vaccinated group while high titers of anti-AVA antibodies but not anti-Spore antibodies existed in the AVA-immunized group. IgG1 and IgG2 were the major subtypes of IgG in both of the two groups. However, the IgG2a level was significantly higher in the A16R group than in the AVA group. At the cellular level, responses of antigen-specific TH2, TH1 and plasma cells were detected. The peripheral TH2 responses could be seen on day 5 after vac- cination, and remained at a high level throughout the experiment (from day 5 post primary immuniza- tion to day 60 post the tertiary immunization); the TH1 responses to A16R vaccine appeared on day 5, while the responses to AVA could only be detected by day 7 after the secondary immunization; a low level of TH1 responses could be observed at the end of the experiment. Antigen-specific plasma cells could be found in the peripheral blood of both the immunized groups, however, the responses in the A16R group appeared earlier, lasted longer, and shown an ascending tendency until the end of the ex- periment when the plasma cell responses in the AVA group were reduced to a very low level. The re- sults suggest that the multiple antigen containing A16R live spore vaccine induces better immune re- sponses than AVA. Combined with serum antibody titers, TH2, TH1 and plasma cell responses could be used as immunological parameters for the evaluation of vaccine efficacy. These findings may afford new insight into the early evaluation of vaccination as well as being a powerful strategy for

  1. Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors.

    Science.gov (United States)

    Wang, Hai-Chao; An, Huai-Jie; Yu, Yun-Zhou; Xu, Qing

    2015-02-01

    DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax.

  2. Producing, controlling, and stabilizing Pasteur's anthrax vaccine: creating a new industry and a health market.

    Science.gov (United States)

    Cassier, Maurice

    2008-06-01

    When Pasteur and Chamberland hastily set up their small biological industry to meet the agricultural demand for the anthrax vaccine, their methods for preparation and production had not yet been stabilized. The process of learning how to standardize biological products was accelerated in 1882 when vaccination accidents required the revision of production norms as the first hypotheses on fixity, inalterability, and transportability of vaccines were invalidated and replaced by procedures for continuous monitoring of the calibration of vaccines and the renewal of vaccine strains. Initially, the incompleteness and ongoing development of production standards justified Pasteur's monopoly on the production of the anthrax vaccine under his immediate supervision. Later on, the Pasteur Institute maintained control of these standards in the framework of a commercial monopoly that it established on the veterinary vaccines first sent and then cultivated abroad by the Société de Vulgarisation du Vaccin Charbonneux Pasteur, founded in 1886.

  3. Quantitative Determination of Lethal Toxin Proteins in Culture Supernatant of Human Live Anthrax Vaccine Bacillus anthracis A16R.

    Science.gov (United States)

    Zai, Xiaodong; Zhang, Jun; Liu, Ju; Liu, Jie; Li, Liangliang; Yin, Ying; Fu, Ling; Xu, Junjie; Chen, Wei

    2016-02-25

    Bacillus anthracis (B. anthracis) is the etiological agent of anthrax affecting both humans and animals. Anthrax toxin (AT) plays a major role in pathogenesis. It includes lethal toxin (LT) and edema toxin (ET), which are formed by the combination of protective antigen (PA) and lethal factor (LF) or edema factor (EF), respectively. The currently used human anthrax vaccine in China utilizes live-attenuated B. anthracis spores (A16R; pXO1+, pXO2-) that produce anthrax toxin but cannot produce the capsule. Anthrax toxins, especially LT, have key effects on both the immunogenicity and toxicity of human anthrax vaccines. Thus, determining quantities and biological activities of LT proteins expressed by the A16R strain is meaningful. Here, we explored LT expression patterns of the A16R strain in culture conditions using another vaccine strain Sterne as a control. We developed a sandwich ELISA and cytotoxicity-based method for quantitative detection of PA and LF. Expression and degradation of LT proteins were observed in culture supernatants over time. Additionally, LT proteins expressed by the A16R and Sterne strains were found to be monomeric and showed cytotoxic activity, which may be the main reason for side effects of live anthrax vaccines. Our work facilitates the characterization of anthrax vaccines components and establishment of a quality control standard for vaccine production which may ultimately help to ensure the efficacy and safety of the human anthrax vaccine A16R.

  4. Anthrax vaccine adsorbed: further evidence supporting continuing the vaccination series rather than restarting the series when doses are delayed.

    Science.gov (United States)

    Pittman, Phillip R; Cavicchia, M A; Kingsbury, J L; Johnson, N A; Barrera-Oro, J G; Schmader, T; Korman, L; Quinn, X; Ranadive, M

    2014-09-03

    Whether to restart or continue the series when anthrax vaccine doses are missed is a frequent medical management problem. We applied the noninferiority analysis model to this prospective study comparing the Bacillus anthracis protective antigen (PA) IgG antibody response and lethal toxin neutralization activity at day 28 to the anthrax vaccine adsorbed (AVA) (Biothrax®) administered on schedule or delayed. A total of 600 volunteers were enrolled: 354 in the on-schedule cohort; 246 in the delayed cohort. Differences were noted in immune responses between cohorts (panthrax vaccine are delayed as long as 5 or more years.

  5. Immunoproteomically identified GBAA_0345, alkyl hydroperoxide reductase subunit C is a potential target for multivalent anthrax vaccine.

    Science.gov (United States)

    Kim, Yeon Hee; Kim, Kyung Ae; Kim, Yu-Ri; Choi, Min Kyung; Kim, Hye Kyeong; Choi, Ki Ju; Chun, Jeong-Hoon; Cha, Kiweon; Hong, Kee-Jong; Lee, Na Gyong; Yoo, Cheon-Kwon; Oh, Hee-Bok; Kim, Tae Sung; Rhie, Gi-eun

    2014-01-01

    Anthrax is caused by the spore-forming bacterium Bacillus anthracis, which has been used as a weapon for bioterrorism. Although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. High rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. To identify novel vaccine candidates, we applied an immunoproteomics approach. Using sera from convalescent guinea pigs or from human patients with anthrax, we identified 34 immunogenic proteins from the virulent B. anthracis H9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, rGBAA_0345 (alkyl hydroperoxide reductase subunit C) and rGBAA_3990 (malonyl CoA-acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent-spore challenge. Moreover, combined vaccination with rGBAA_0345 and rPA (protective antigen) exhibited an enhanced ability to protect against anthrax mortality. Finally, we demonstrated that GBAA_0345 localizes to anthrax spores and bacilli. Our results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination. This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells.

  6. Comprehensive analysis and selection of anthrax vaccine adsorbed immune correlates of protection in rhesus macaques.

    Science.gov (United States)

    Chen, Ligong; Schiffer, Jarad M; Dalton, Shannon; Sabourin, Carol L; Niemuth, Nancy A; Plikaytis, Brian D; Quinn, Conrad P

    2014-11-01

    Humoral and cell-mediated immune correlates of protection (COP) for inhalation anthrax in a rhesus macaque (Macaca mulatta) model were determined. The immunological and survival data were from 114 vaccinated and 23 control animals exposed to Bacillus anthracis spores at 12, 30, or 52 months after the first vaccination. The vaccinated animals received a 3-dose intramuscular priming series (3-i.m.) of anthrax vaccine adsorbed (AVA) (BioThrax) at 0, 1, and 6 months. The immune responses were modulated by administering a range of vaccine dilutions. Together with the vaccine dilution dose and interval between the first vaccination and challenge, each of 80 immune response variables to anthrax toxin protective antigen (PA) at every available study time point was analyzed as a potential COP by logistic regression penalized by least absolute shrinkage and selection operator (LASSO) or elastic net. The anti-PA IgG level at the last available time point before challenge (last) and lymphocyte stimulation index (SI) at months 2 and 6 were identified consistently as a COP. Anti-PA IgG levels and lethal toxin neutralization activity (TNA) at months 6 and 7 (peak) and the frequency of gamma interferon (IFN-γ)-secreting cells at month 6 also had statistically significant positive correlations with survival. The ratio of interleukin 4 (IL-4) mRNA to IFN-γ mRNA at month 6 also had a statistically significant negative correlation with survival. TNA had lower accuracy as a COP than did anti-PA IgG response. Following the 3-i.m. priming with AVA, the anti-PA IgG responses at the time of exposure or at month 7 were practicable and accurate metrics for correlating vaccine-induced immunity with protection against inhalation anthrax.

  7. Combination of two candidate subunit vaccine antigens elicits protective immunity to ricin and anthrax toxin in mice.

    Science.gov (United States)

    Vance, David J; Rong, Yinghui; Brey, Robert N; Mantis, Nicholas J

    2015-01-09

    In an effort to develop combination vaccines for biodefense, we evaluated a ricin subunit antigen, RiVax, given in conjunction with an anthrax protective antigen, DNI. The combination led to high endpoint titer antibody response, neutralizing antibodies, and protective immunity against ricin and anthrax lethal toxin. This is a natural combination vaccine, since both antigens are recombinant subunit proteins that would be given to the same target population.

  8. Vaccine-induced protection against anthrax in cheetah (Acinonyx jubatus) and black rhinoceros (Diceros bicornis).

    Science.gov (United States)

    Turnbull, P C B; Tindall, B W; Coetzee, J D; Conradie, C M; Bull, R L; Lindeque, P M; Huebschle, O J B

    2004-09-03

    Institution of a policy of vaccination in endangered species with a vaccine not previously administered to it cannot be undertaken lightly. This applies even more in the case of cheetah (Acinonyx jubatus) with their unusually monomorphic gene pool and the potential restrictions this places on their immune responses. However, the recently observed mortalities from anthrax in these animals in the Etosha National Park, Namibia, made it imperative to evaluate vaccination. Black rhinoceros (Diceros bicornis), another endangered species in the park, have been vaccinated for over three decades but the effectiveness of this has never been evaluated. Passive protection tests in A/J mice using sera from 12 cheetahs together with enzyme immunoassay indicated that cheetah are able to mount seemingly normal primary and secondary humoral immune responses to the Sterne 34F2 live spore livestock vaccine. Overall protection rates in mice injected with the sera rose and fell in concert with rises and declines in antibody titres, although fine analysis showed that the correlation between titre and protection was complex. Once a high level of protection (96% of mice 1 month after a second booster in the cheetahs) had been achieved, the duration of substantial protection appeared good (60% of the mice 5 months after the second booster). Protection conferred on mice by sera from three of four vaccinated rhino was almost complete, but, obscurely, none of the mice receiving serum from the fourth rhino were protected. Sera from three park lions with naturally acquired high antibody titres, included as controls, also conferred high levels of protection. For the purposes of wildlife management, the conclusions were that vaccination of cheetah with the standard animal anthrax vaccine causes no observable ill effect in the animals and does appear to confer protective immunity. At least one well-separated booster does appear to be desirable. Vaccination of rhino also appears to be justified

  9. A viral nanoparticle with dual function as an anthrax antitoxin and vaccine.

    Directory of Open Access Journals (Sweden)

    Darly J Manayani

    2007-10-01

    Full Text Available The recent use of Bacillus anthracis as a bioweapon has stimulated the search for novel antitoxins and vaccines that act rapidly and with minimal adverse effects. B. anthracis produces an AB-type toxin composed of the receptor-binding moiety protective antigen (PA and the enzymatic moieties edema factor and lethal factor. PA is a key target for both antitoxin and vaccine development. We used the icosahedral insect virus Flock House virus as a platform to display 180 copies of the high affinity, PA-binding von Willebrand A domain of the ANTXR2 cellular receptor. The chimeric virus-like particles (VLPs correctly displayed the receptor von Willebrand A domain on their surface and inhibited lethal toxin action in in vitro and in vivo models of anthrax intoxication. Moreover, VLPs complexed with PA elicited a potent toxin-neutralizing antibody response that protected rats from anthrax lethal toxin challenge after a single immunization without adjuvant. This recombinant VLP platform represents a novel and highly effective, dually-acting reagent for treatment and protection against anthrax.

  10. Changing patterns of human anthrax in Azerbaijan during the post-Soviet and preemptive livestock vaccination eras.

    Directory of Open Access Journals (Sweden)

    Ian Kracalik

    2014-07-01

    Full Text Available We assessed spatial and temporal changes in the occurrence of human anthrax in Azerbaijan during 1984 through 2010. Data on livestock outbreaks, vaccination efforts, and human anthrax incidence during Soviet governance, post-Soviet governance, preemptive livestock vaccination were analyzed. To evaluate changes in the spatio-temporal distribution of anthrax, we used a combination of spatial analysis, cluster detection, and weighted least squares segmented regression. Results indicated an annual percent change in incidence of (+11.95% from 1984 to 1995 followed by declining rate of -35.24% after the initiation of livestock vaccination in 1996. Our findings also revealed geographic variation in the spatial distribution of reporting; cases were primarily concentrated in the west early in the study period and shifted eastward as time progressed. Over twenty years after the dissolution of the Soviet Union, the distribution of human anthrax in Azerbaijan has undergone marked changes. Despite decreases in the incidence of human anthrax, continued control measures in livestock are needed to mitigate its occurrence. The shifting patterns of human anthrax highlight the need for an integrated "One Health" approach that takes into account the changing geographic distribution of the disease.

  11. Changing patterns of human anthrax in Azerbaijan during the post-Soviet and preemptive livestock vaccination eras.

    Science.gov (United States)

    Kracalik, Ian; Abdullayev, Rakif; Asadov, Kliment; Ismayilova, Rita; Baghirova, Mehriban; Ustun, Narmin; Shikhiyev, Mazahir; Talibzade, Aydin; Blackburn, Jason K

    2014-07-01

    We assessed spatial and temporal changes in the occurrence of human anthrax in Azerbaijan during 1984 through 2010. Data on livestock outbreaks, vaccination efforts, and human anthrax incidence during Soviet governance, post-Soviet governance, preemptive livestock vaccination were analyzed. To evaluate changes in the spatio-temporal distribution of anthrax, we used a combination of spatial analysis, cluster detection, and weighted least squares segmented regression. Results indicated an annual percent change in incidence of (+)11.95% from 1984 to 1995 followed by declining rate of -35.24% after the initiation of livestock vaccination in 1996. Our findings also revealed geographic variation in the spatial distribution of reporting; cases were primarily concentrated in the west early in the study period and shifted eastward as time progressed. Over twenty years after the dissolution of the Soviet Union, the distribution of human anthrax in Azerbaijan has undergone marked changes. Despite decreases in the incidence of human anthrax, continued control measures in livestock are needed to mitigate its occurrence. The shifting patterns of human anthrax highlight the need for an integrated "One Health" approach that takes into account the changing geographic distribution of the disease.

  12. Anthrax vaccination induced anti-lethal factor IgG: fine specificity and neutralizing capacity.

    Science.gov (United States)

    Crowe, Sherry R; Garman, Lori; Engler, Renata J M; Farris, A Darise; Ballard, Jimmy D; Harley, John B; James, Judith A

    2011-05-09

    The efficacy biomarker of the currently licensed anthrax vaccine (AVA) is based on quantity and neutralizing capacity of anti-protective antigen (anti-PA) antibodies. However, animal studies have demonstrated that antibodies to lethal factor (LF) can provide protection against in vivo bacterial spore challenges. Improved understanding of the fine specificities of humoral immune responses that provide optimum neutralization capacity may enhance the efficacy of future passive immune globulin preparations to treat and prevent inhalation anthrax morbidity and mortality. This study (n=1000) was designed to identify AVA vaccinated individuals who generate neutralizing antibodies and to determine what specificities correlate with protection. The number of vaccine doses, years post vaccination, and PA titer were associated with in vitro neutralization, reinforcing previous reports. In addition, African American individuals had lower serologic neutralizing activity than European Americans, suggesting a genetic role in the generation of these neutralizing antibodies. Of the vaccinated individuals, only 69 (6.9%) had moderate levels of anti-LF IgG compared to 244 (24.4%) with low and 687 (68.7%) with extremely low levels of IgG antibodies to LF. Using overlapping decapeptide analysis, we identified six common LF antigenic regions targeted by those individuals with moderate levels of antibodies to LF and high in vitro toxin neutralizing activity. Affinity purified antibodies directed against antigenic epitopes within the PA binding and ADP-ribotransferase-like domains of LF were able to protect mice against lethal toxin challenge. Findings from these studies have important implications for vaccine design and immunotherapeutic development.

  13. Generation of protective immune response against anthrax by oral immunization with protective antigen plant-based vaccine.

    Science.gov (United States)

    Gorantala, Jyotsna; Grover, Sonam; Rahi, Amit; Chaudhary, Prerna; Rajwanshi, Ravi; Sarin, Neera Bhalla; Bhatnagar, Rakesh

    2014-04-20

    In concern with frequent recurrence of anthrax in endemic areas and inadvertent use of its spores as biological weapon, the development of an effective anthrax vaccine suitable for both human and veterinary needs is highly desirable. A simple oral delivery through expression in plant system could offer promising alternative to the current methods that rely on injectable vaccines extracted from bacterial sources. In the present study, we have expressed protective antigen (PA) gene in Indian mustard by Agrobacterium-mediated transformation and in tobacco by plastid transformation. Putative transgenic lines were verified for the presence of transgene and its expression by molecular analysis. PA expressed in transgenic lines was biologically active as evidenced by macrophage lysis assay. Intraperitoneal (i.p.) and oral immunization with plant PA in murine model indicated high serum PA specific IgG and IgA antibody titers. PA specific mucosal immune response was noted in orally immunized groups. Further, antibodies indicated lethal toxin neutralizing potential in-vitro and conferred protection against in-vivo toxin challenge. Oral immunization experiments demonstrated generation of immunoprotective response in mice. Thus, our study examines the feasibility of oral PA vaccine expressed in an edible plant system against anthrax.

  14. Development of a Sterne-based Complement Fixation Test to monitor the humoral response induced by anthrax vaccines

    Directory of Open Access Journals (Sweden)

    Rosanna eAdone

    2016-01-01

    Full Text Available Anthrax is a zoonotic disease caused by Bacillus anthracis spore-forming bacterium. Since it is primarily a disease of animals, the control in animals and humans depends on the prevention in livestock, principally cattle, sheep and goats. Most veterinary vaccines utilize the toxigenic, uncapsulated (pXO1+/pXO2– B.anthracis strain 34F2 which affords protection through the production of neutralizing antibodies directed to the toxin components Protective Antigen (PA, Lethal Factor (LF and Edema Factor (EF. The titration of specific antibodies in sera of vaccinated animals is crucial to evaluate the efficacy of the vaccination and to obtain epidemiological information for an effective anthrax surveillance. In this study, we developed a Sterne-based Complement Fixation Test to detect specific antibodies induced in animals vaccinated with Sterne 34F2 . We assessed its efficacy in laboratory animals and under field conditions by monitoring the humoral response induced by vaccination in cattle. The results indicated that the Sterne-based CFT is able to identify vaccinated animals with a good sensitivity and specificity offering many benefits especially with regard to costs, standardization and reproducibility of the assay procedure.

  15. Development of a Sterne-Based Complement Fixation Test to Monitor the Humoral Response Induced by Anthrax Vaccines

    Science.gov (United States)

    Adone, Rosanna; Sali, Michela; Francia, Massimiliano; Iatarola, Michela; Donatiello, Adelia; Fasanella, Antonio

    2016-01-01

    Anthrax is a zoonotic disease caused by Bacillus anthracis spore-forming bacterium. Since it is primarily a disease of animals, the control in animals, and humans depend on the prevention in livestock, principally cattle, sheep, and goats. Most veterinary vaccines utilize the toxigenic, uncapsulated (pXO1+/pXO2–) B. anthracis strain 34F2 which affords protection through the production of neutralizing antibodies directed to the toxin components Protective Antigen (PA), Lethal Factor (LF), and Edema Factor (EF). The titration of specific antibodies in sera of vaccinated animals is crucial to evaluate the efficacy of the vaccination and to obtain epidemiological information for an effective anthrax surveillance. In this study, we developed a Sterne-based Complement Fixation Test (CFT) to detect specific antibodies induced in animals vaccinated with Sterne 34F2. We assessed its efficacy in laboratory animals and under field conditions by monitoring the humoral response induced by vaccination in cattle. The results indicated that the Sterne-based CFT is able to correctly identify vaccinated animals. It proved to be a very sensitive and specific test. Moreover, the Sterne-based CFT offers many benefits with regard to costs, standardization and reproducibility of the assay procedure. PMID:26858700

  16. The public science of Louis Pasteur: the experiment on anthrax vaccine in the popular press of the time.

    Science.gov (United States)

    Bucchi, M

    1997-01-01

    The paper focuses on Pasteur's public experimentation of the anthrax vaccine (Pouilly-le-Fort, 1881) as portrayed in the English and French popular press of the time. It is argued that this 'popular' level of representation did not merely provide additional publicity for Pasteur's ideas. Rather, the nature and meaning of the experiment itself and of the related controversy on immunisation were substantially negotiated and shaped within the public arena. The multifold consequences of this framing at the public level are explored. In particular, attention is drawn to the relationships that in such process were established with other issues debated at the same time in the arena, namely homeopathy, vivisection and vaccination.

  17. Anthrax: Diagnosis

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Anthrax Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Anthrax Basic Information Types of Anthrax Cutaneous Anthrax Inhalation ...

  18. Anthrax Pathogenesis.

    Science.gov (United States)

    Moayeri, Mahtab; Leppla, Stephen H; Vrentas, Catherine; Pomerantsev, Andrei P; Liu, Shihui

    2015-01-01

    Anthrax is caused by the spore-forming, gram-positive bacterium Bacillus anthracis. The bacterium's major virulence factors are (a) the anthrax toxins and (b) an antiphagocytic polyglutamic capsule. These are encoded by two large plasmids, the former by pXO1 and the latter by pXO2. The expression of both is controlled by the bicarbonate-responsive transcriptional regulator, AtxA. The anthrax toxins are three polypeptides-protective antigen (PA), lethal factor (LF), and edema factor (EF)-that come together in binary combinations to form lethal toxin and edema toxin. PA binds to cellular receptors to translocate LF (a protease) and EF (an adenylate cyclase) into cells. The toxins alter cell signaling pathways in the host to interfere with innate immune responses in early stages of infection and to induce vascular collapse at late stages. This review focuses on the role of anthrax toxins in pathogenesis. Other virulence determinants, as well as vaccines and therapeutics, are briefly discussed.

  19. Analysis of pregnancy and infant health outcomes among women in the National Smallpox Vaccine in Pregnancy Registry who received Anthrax Vaccine Adsorbed.

    Science.gov (United States)

    Conlin, Ava Marie S; Bukowinski, Anna T; Gumbs, Gia R

    2015-08-26

    The National Smallpox Vaccine in Pregnancy Registry (NSVIPR) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. Approximately 65% of NSVIPR participants also inadvertently received Anthrax Vaccine Adsorbed (AVA) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. AVA-exposed pregnancies were ascertained using NSVIPR and electronic healthcare data. Rates of pregnancy loss and infant health outcomes, including major birth defects, were compared between AVA-exposed and AVA-unexposed pregnancies. Analyses included AVA-exposed and AVA-unexposed pregnant women who also received smallpox vaccine 28 days prior to or during pregnancy. Rates of adverse outcomes among the AVA-exposed group were similar to or lower than expected when compared with published reference rates and the AVA-unexposed population. The findings provide reassurance of the safety of AVA when inadvertently received by a relatively young and healthy population during pregnancy.

  20. Protein- and DNA-based anthrax toxin vaccines confer protection in guinea pigs against inhalational challenge with Bacillus cereus G9241.

    Science.gov (United States)

    Palmer, John; Bell, Matt; Darko, Christian; Barnewall, Roy; Keane-Myers, Andrea

    2014-11-01

    In the past decade, several Bacillus cereus strains have been isolated from otherwise healthy individuals who succumbed to bacterial pneumonia presenting symptoms resembling inhalational anthrax. One strain was indistinguishable from B. cereus G9241, previously cultured from an individual who survived a similar pneumonia-like illness and which was shown to possess a complete set of plasmid-borne anthrax toxin-encoding homologs. The finding that B. cereus G9241 pathogenesis in mice is dependent on pagA1-derived protective antigen (PA) synthesis suggests that an anthrax toxin-based vaccine may be effective against this toxin-encoding B. cereus strain. Dunkin Hartley guinea pigs were immunized with protein- and DNA-based anthrax toxin-based vaccines, immune responses were evaluated and survival rates were calculated after lethal aerosol exposure with B. cereus G9241 spores. Each vaccine induced seroconversion with the protein immunization regimen eliciting significantly higher serum levels of antigen-specific antibodies at the prechallenge time-point compared with the DNA-protein prime-boost immunization schedule. Complete protection against lethal challenge was observed in all groups with a detectable prechallenge serum titer of toxin neutralizing antibodies. For the first time, we demonstrated that the efficacy of fully defined anthrax toxin-based vaccines was protective against lethal B. cereus G9241 aerosol challenge in the guinea pig animal model.

  1. Enhanced Early Innate and T Cell-mediated Responses in Subjects Immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909)

    OpenAIRE

    Minang, Jacob T.; Inglefield, Jon R.; Harris, Andrea M.; Lathey, Janet L.; Alleva, David G.; Sweeney, Diane L.; Hopkins, Robert J.; Lacy, Michael J.; Bernton, Edward W.

    2014-01-01

    NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a Phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax® (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24 to 48 hours...

  2. Glassy-state stabilization of a dominant negative inhibitor anthrax vaccine containing aluminum hydroxide and glycopyranoside lipid A adjuvants.

    Science.gov (United States)

    Hassett, Kimberly J; Vance, David J; Jain, Nishant K; Sahni, Neha; Rabia, Lilia A; Cousins, Megan C; Joshi, Sangeeta; Volkin, David B; Middaugh, C Russell; Mantis, Nicholas J; Carpenter, John F; Randolph, Theodore W

    2015-02-01

    During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses. To better understand and prevent such losses, dominant negative inhibitor (DNI), a recombinant protein antigen for a candidate vaccine against anthrax, was formulated as a liquid and as a glassy lyophilized powder with the adjuvants aluminum hydroxide and glycopyranoside lipid A (GLA). Freeze-thawing of the liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity in mice. Immunogenicity of liquid vaccines also decreased when stored at 40°C for 8 weeks, as measured by decreases in neutralizing antibody titers in vaccinated mice. Concomitant with efficacy losses at elevated temperatures, changes in DNI structure were detected by fluorescence spectroscopy and increased deamidation was observed by capillary isoelectric focusing (cIEF) after only 1 week of storage of the liquid formulation at 40°C. In contrast, upon lyophilization, no additional deamidation after 4 weeks at 40°C and no detectable changes in DNI structure or reduction in immunogenicity after 16 weeks at 40°C were observed. Vaccines containing aluminum hydroxide and GLA elicited higher immune responses than vaccines adjuvanted with only aluminum hydroxide, with more mice responding to a single dose.

  3. Anthrax Basics

    Science.gov (United States)

    ... Recommend on Facebook Tweet Share Compartir What is anthrax? Anthrax is a serious infectious disease caused by ... or flu. How do animals get infected with anthrax? Domestic and wild animals such as cattle, sheep, ...

  4. Inhalational anthrax (Ames aerosol in naive and vaccinated New Zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia.

    Directory of Open Access Journals (Sweden)

    Bradford eGutting

    2012-06-01

    Full Text Available There is a need to better understand inhalational anthrax in relevant animal models. This understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. The aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (>100LD50 of Bacillus anthracis (Ames spores immediately following exposure through 36 hours. The primary goal of collecting the data was to support investigators in developing computational models of inhalational anthrax disease. Rabbits were vaccinated prior to exposure with the human vaccine (Anthrax Vaccine Adsorbed, AVA or were sham-vaccinated, and were then exposed in pairs (1 sham and 1 AVA so disease kinetics could be characterized in equally-dosed hosts where one group is fully protected and is able to clear the infection (AVA-vaccinated, while the other is susceptible to disease, in which case the bacteria are able to escape containment and replicate uncontrolled (sham-vaccinated rabbits. Between 4-5% of the presented aerosol dose was retained in the lung of sham- and AVA-vaccinated rabbits as measured by dilution plate analysis of homogenized lung tissue or bronchoalveolar lavage (BAL fluid. After 6 and 36 hours, >80% and >96%, respectively, of the deposited spores were no longer detected in BAL, with no detectable difference between sham- or AVA-vaccinated rabbits. Thereafter, differences between the two groups became noticeable. In sham-vaccinated rabbits the bacteria were detected in the tracheobronchial lymph nodes (TBLN 12 hours post exposure and in the circulation at 24 hours, a time point which was also associated with dramatic increases in vegetative CFU in the lung tissue of some animals. In all sham-vaccinated rabbits, bacteria increased in both TBLN and blood through 36 hours at which point in time some rabbits succumbed to disease. In contrast, AVA-vaccinated rabbits showed

  5. Health Risk Communication in the Anthrax Vaccine Immunization Program: Lessons for the Future

    Science.gov (United States)

    2001-04-01

    percent lethal if not treated before the onset of symptoms. Once the flu-like symp- toms appear, there is no effective cure . Anthrax has no smell or...like Sudden Infant Death Syndrome, autism , or illnesses among Gulf War veterans. Any illness following a shot may be erro- neously attributed to the

  6. Protective Antigen-Specific Memory B Cells Persist Years after Anthrax Vaccination and Correlate with Humoral Immunity

    Directory of Open Access Journals (Sweden)

    Lori Garman

    2014-08-01

    Full Text Available Anthrax Vaccine Adsorbed (AVA generates short-lived protective antigen (PA specific IgG that correlates with in vitro toxin neutralization and protection from Bacillus anthracis challenge. Animal studies suggest that when PA-specific IgG has waned, survival after spore challenge correlates with an activation of PA-specific memory B cells. Here, we characterize the quantity and the longevity of AVA-induced memory B cell responses in humans. Peripheral blood mononuclear cells (PBMCs from individuals vaccinated ≥3 times with AVA (n = 50 were collected early (3–6 months, n = 27 or late after their last vaccination (2–5 years, n = 23, pan-stimulated, and assayed by ELISPOT for total and PA-specific memory B cells differentiated into antibody secreting cells (ASCs. PA-specific ASC percentages ranged from 0.02% to 6.25% (median: 1.57% and did not differ between early and late post-vaccination individuals. PA-specific ASC percentages correlated with plasma PA-specific IgG (r = 0.42, p = 0.03 and toxin neutralization (r = 0.52, p = 0.003 early post vaccination. PA-specific ASC percentages correlated with supernatant anti-PA both early (r = 0.60, p = 0.001 and late post vaccination (r = 0.71, p < 0.0001. These data suggest PA-specific memory B cell responses are long-lived and can be estimated after recent vaccination by the magnitude and neutralization capacity of the humoral response.

  7. Simultaneous immunization of cattle with foot-and-mouth disease (FMD and live anthrax vaccines do not interfere with FMD booster responses

    Directory of Open Access Journals (Sweden)

    Myrian Trotta

    2015-01-01

    Full Text Available Foot-and-mouth disease (FMD vaccination in Argentina is compulsory for most of the cattle population and conducted by certified veterinarians. This organized campaign may facilitate the controlled application of other vaccines against endemic diseases, provided immune responses against FMD are not hindered. There is no published information on the interference of immunity against FMD vaccines when applied together with a live bacterial vaccine. In this study we evaluated if the simultaneous application of a Bacillus anthracis live vaccine with a commercial tetravalent oil-based FMD vaccine (FMD-vac used in Argentina, modifies the antibody booster responses against FMD virus (FMDV in cattle. Two groups of 16 heifers with comparable liquid phase blocking ELISA (LPBE titers were immunized with the FMD-vac alone or simultaneously with a commercial attenuated bovine anthrax Sterne strain vaccine (ABV. Serum samples were obtained at 0, 25, 60 and 90 days post vaccination (dpv and specific antibodies against two FMDV vaccine strains were assessed by LPBE, avidity and IgG-isotype ELISAs. Bovines immunized with FMD-vac or FMDV-V + ABV responded with a boost in the LPBE antibody titers and avidity at 25 dpv, and remained within similar levels up to the end of the study. Animals vaccinated with FMD-vac + ABV had significantly higher LPBE titers at 25 dpv, compared to those immunized with FMD-vac alone; which was due to an increase in IgG2 titers. Overall, antibody titers elicited in both groups were similar and followed comparable kinetics over time. We conclude that the simultaneous application of a live anthrax vaccine with the current FMD tetravalent vaccine used in Argentina in cattle previously immunized against FMD, did not counteract the serological response induced by FMD vaccination.

  8. Inhalational anthrax (Ames aerosol) in naïve and vaccinated New Zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia.

    Science.gov (United States)

    Gutting, Bradford W; Nichols, Tonya L; Channel, Stephen R; Gearhart, Jeffery M; Andrews, George A; Berger, Alan E; Mackie, Ryan S; Watson, Brent J; Taft, Sarah C; Overheim, Katie A; Sherwood, Robert L

    2012-01-01

    There is a need to better understand inhalational anthrax in relevant animal models. This understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. The aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (> 100 LD(50)) of Bacillus anthracis (Ames) spores immediately following exposure through 36 h. The primary goal of collecting the data was to support investigators in developing computational models of inhalational anthrax disease. Rabbits were vaccinated prior to exposure with the human vaccine (Anthrax Vaccine Adsorbed, AVA) or were sham-vaccinated, and were then exposed in pairs (one sham and one AVA) so disease kinetics could be characterized in equally-dosed hosts where one group is fully protected and is able to clear the infection (AVA-vaccinated), while the other is susceptible to disease, in which case the bacteria are able to escape containment and replicate uncontrolled (sham-vaccinated rabbits). Between 4-5% of the presented aerosol dose was retained in the lung of sham- and AVA-vaccinated rabbits as measured by dilution plate analysis of homogenized lung tissue or bronchoalveolar lavage (BAL) fluid. After 6 and 36 h, >80% and >96%, respectively, of the deposited spores were no longer detected in BAL, with no detectable difference between sham- or AVA-vaccinated rabbits. Thereafter, differences between the two groups became noticeable. In sham-vaccinated rabbits the bacteria were detected in the tracheobronchial lymph nodes (TBLN) 12 h post-exposure and in the circulation at 24 h, a time point which was also associated with dramatic increases in vegetative CFU in the lung tissue of some animals. In all sham-vaccinated rabbits, bacteria increased in both TBLN and blood through 36 h at which point in time some rabbits succumbed to disease. In contrast, AVA-vaccinated rabbits showed small numbers of CFU in

  9. Anthrax: Symptoms

    Science.gov (United States)

    ... EID Journal Articles Anthrax-Related MMWRs Medscape Commentaries Symptoms Language: English Español (Spanish) Recommend on Facebook Tweet ... cause severe illness and even death. Cutaneous anthrax symptoms can include: A group of small blisters or ...

  10. Effect of delayed anthrax vaccine dose on Bacillus anthracis protective antigen IgG response and lethal toxin neutralization activity.

    Science.gov (United States)

    Pittman, Phillip R; Fisher, Diana; Quinn, Xiaofei; Schmader, Trevor; Barrera-Oro, Julio G

    2013-10-17

    We describe the Bacillus anthracis protective antigen IgG antibody response and the B. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (AVA, BioThrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti-PA IgG before the boost, compared to 99.2% (P<0.0001) 28 days after the boost. Geometric mean anti-PA IgG concentration (GMC) was 1.66 μg/mL before and 887.82 μg/mL after the boost (P<0.0001). The proportion of individuals with four-fold increase in GMC following the boost ranged from 93.8% to 100%. Robust anti-PA IgG levels and B. anthracis lethal toxin neutralization activity are induced when an AVA dose is delayed as long as two years. These data support continuing with the vaccination schedule when a dose is delayed as long as two years rather than restarting the series.

  11. Anthrax and Other Vaccines: Use in the U.S. Military

    Science.gov (United States)

    2013-05-16

    effective with fewer adverse effects than antibiotics or other treatments – Enable force projection by providing continuous, long-lasting protection...Botulinum Toxoids* • Tularemia Vaccine* • Smallpox vaccine (Vaccinia Virus, Cell Culture-derived)* • Equine Encephalitis Virus Vaccines* *Investigational New...DATSD(CBD) Medical Biological Defense: Current Capabilities – Therapeutics • Therapeutics – Various antibiotics for treatment of exposure to

  12. Phase I study of safety and immunogenicity of an Escherichia coli-derived recombinant protective antigen (rPA vaccine to prevent anthrax in adults.

    Directory of Open Access Journals (Sweden)

    Bruce K Brown

    Full Text Available BACKGROUND: The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA. METHODOLOGY/PRINCIPAL FINDINGS: A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29 was observed in the group receiving 25 µg Alhydrogel®-formulated rPA. CONCLUSIONS/SIGNIFICANCE: The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00057525.

  13. Marked enhancement of the immune response to BioThrax® (Anthrax Vaccine Adsorbed) by the TLR9 agonist CPG 7909 in healthy volunteers.

    Science.gov (United States)

    Rynkiewicz, Dianna; Rathkopf, Melinda; Sim, Iain; Waytes, A Thomas; Hopkins, Robert J; Giri, Lallan; DeMuria, Deborah; Ransom, Janet; Quinn, James; Nabors, Gary S; Nielsen, Carl J

    2011-08-26

    Immunization with BioThrax(®) (Anthrax Vaccine Adsorbed) is a safe and effective means of preventing anthrax. Animal studies have demonstrated that the addition of CpG DNA adjuvants to BioThrax can markedly increase the immunogenicity of the vaccine, increasing both serum anti-protective antigen (PA) antibody and anthrax toxin-neutralizing antibody (TNA) concentrations. The immune response to CpG-adjuvanted BioThrax in animals was not only stronger, but was also more rapid and led to higher levels of protection in spore challenge models. The B-class CpG DNA adjuvant CPG 7909, a 24-base synthetic, single-strand oligodeoxynucleotide, was evaluated for its safety profile and adjuvant properties in a Phase 1 clinical trial. A double-blind study was performed in which 69 healthy subjects, age 18-45 years, were randomized to receive three doses of either: (1) BioThrax alone, (2) 1 mg of CPG 7909 alone or (3) BioThrax plus 1 mg of CPG 7909, all given intramuscularly on study days 0, 14 and 28. Subjects were monitored for IgG to PA by ELISA and for TNA titers through study day 56 and for safety through month 6. CPG 7909 increased the antibody response by 6-8-fold at peak, and accelerated the response by 3 weeks compared to the response seen in subjects vaccinated with BioThrax alone. No serious adverse events related to study agents were reported, and the combination was considered to be reasonably well tolerated. The marked acceleration and enhancement of the immune response seen by combining BioThrax and CPG 7909 offers the potential to shorten the course of immunization and reduce the time to protection, and may be particularly useful in the setting of post-exposure prophylaxis.

  14. Anthrax Remembered

    Centers for Disease Control (CDC) Podcasts

    2015-08-03

    Dr. John Jernigan and Dr. D. Peter Drotman recall the 2001 anthrax attacks and rapid publication of the landmark paper reporting the initial cases of inhalational anthrax.  Created: 8/3/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/3/2015.

  15. Military Hospitalizations among Deployed US Service Members Following Anthrax Vaccination, 1998-2001

    Science.gov (United States)

    2006-04-01

    and hospitalizations for a wide range of outcomes. Cox propor- tional hazards models could not be run for systemic lupus erythematosus , fibromyalgia...sclerosis, systemic lupus erythematosus , or fibromyalgia. Vaccine safety within military populations remains an important issue, and further study is...Reporting System (VAERS). Pharmacoepidemiol Drug Saf 2004; 13:825-40. 14. Lange JL, Lesikar SE, Rubertone MV, Brundage JF. Comprehensive systematic

  16. Oral Vaccination Against Anthrax Using a Transgenic Plant Expressing Protective Antigen.

    Science.gov (United States)

    1996-09-01

    need for effective vaccines which will induce the mucosal immunity system against this highly lethal human pathogen. Characterization of virulence factor...colonizing the mucosal tissue in the gut and therefore may induce mucosal immunity to F I antigen through association with the Peyer’s patches... mucosal immunity , the antigen must first be stable in the gut and then be able to penetrate the epithelial cells to facilitate absorption by M cells. For

  17. Cutaneous anthrax (image)

    Science.gov (United States)

    Anthrax is caused by the bacteria Bacillus anthracis . While anthrax commonly affects hoofed animals such as sheep and goats, humans may get sick from anthrax, too. The most common type of anthrax infection ...

  18. Human Cutaneous Anthrax, Georgia 2010–2012

    Science.gov (United States)

    Kracalik, Ian; Malania, Lile; Tsertsvadze, Nikoloz; Manvelyan, Julietta; Bakanidze, Lela; Imnadze, Paata; Tsanava, Shota

    2014-01-01

    We assessed the occurrence of human cutaneous anthrax in Georgia during 2010–-2012 by examining demographic and spatial characteristics of reported cases. Reporting increased substantially, as did clustering of cases near urban centers. Control efforts, including education about anthrax and livestock vaccination, can be directed at areas of high risk. PMID:24447721

  19. Human cutaneous anthrax, Georgia 2010-2012.

    Science.gov (United States)

    Kracalik, Ian; Malania, Lile; Tsertsvadze, Nikoloz; Manvelyan, Julietta; Bakanidze, Lela; Imnadze, Paata; Tsanava, Shota; Blackburn, Jason K

    2014-02-01

    We assessed the occurrence of human cutaneous anthrax in Georgia during 2010--2012 by examining demographic and spatial characteristics of reported cases. Reporting increased substantially, as did clustering of cases near urban centers. Control efforts, including education about anthrax and livestock vaccination, can be directed at areas of high risk.

  20. Anthrax - past, present and future

    Directory of Open Access Journals (Sweden)

    Madle-Samardžija Nadežda D.

    2002-01-01

    Full Text Available History Anthrax has been known since ancient times. Besides some references in the Old Testament, there is evidence of plagues in ancient Egypt, as well as descriptions of the disease by the Roman poet Virgil. Etiology Anthrax is caused by Bacillus anthracis, unmovable, aerobic, gram-positive rods. It forms spores, which can survive for years in the environment. Pathogenesis Capsular polypeptide and anthrax toxin are the principal virulence factors of Bacillus anthracis. Anthrax toxin consists of three proteins called protective antigen, edema factor, and lethal factor. It is thought that the inflammatory mediator - lethal factor is stored within the macrophage during the early stage of infection. It is rapidly released in large amounts into the blood stream and once the threshold for lysis is reached, it may be the cause of sudden death. Epidemiology Grass-eating animals are usually infected by the bacilli from grass and ground. The disease is transmitted to people by contact with the sick animals or their products, such as wool skin, meat etc. Clinical features Two clinical forms exist: outer cutaneous and inner, including inhalation and gastrointestinal anthrax. While cutaneous anthrax is easily cured, the inner forms have high mortality rates. Diagnosis and differential diagnosis The diagnosis is easily established in cutaneous cases, characterized by black eschar. Severe intoxication and collapse during the course of bronchopneumonia or hemorrhagic enteritis should arise suspicion of anthrax. Therapy Hospitalization of patients is mandatory. Bacillus anthracis is susceptible to a number of antibiotics, including penicillin, erythromycin tetracyclines, cephalosporins etc. Prevention General veterinary prevention including vaccination of livestock and control of products is very important. The vaccine consists of anthrax bacillus that is attenuated. The endangered population, such as animal workers and military personnel should be vaccinated

  1. Enhanced early innate and T cell-mediated responses in subjects immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909).

    Science.gov (United States)

    Minang, Jacob T; Inglefield, Jon R; Harris, Andrea M; Lathey, Janet L; Alleva, David G; Sweeney, Diane L; Hopkins, Robert J; Lacy, Michael J; Bernton, Edward W

    2014-11-28

    NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax(®) (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24-48 h after administration of AV7909 formulations, returning to baseline by Day 7. AVA (no CPG 7909) resulted in elevated IL-6 and CRP, but not IP-10. Another marker of CpG, transiently decreased absolute lymphocyte counts (ALCs), correlated with transiently increased IP-10. Cellular recall responses to anthrax protective antigen (PA) or PA peptides were assessed by IFN-γ ELISpot assay performed on cryopreserved PBMCs obtained from subjects prior to immunization and 7 days following the second immunization (study day 21). One-half of subjects that received AV7909 with low-dose (0.25mg/dose) CPG 7909 possessed positive Day 21 T cell responses to PA. In contrast, positive T cell responses occurred at an 11% average rate (1/9) for AVA-treated subjects. Differences in cellular responses due to dose level of CPG 7909 were not associated with differences in humoral anti-PA IgG responses, which were elevated for recipients of AV7909 compared to recipients of AVA. Serum markers at 24 or 48 h (i.e. % ALC decrease, or increase in IL-6, IP-10, or CRP) correlated with the humoral (antibody) responses 1 month later, but did not correlate with cellular ELISpot responses. In summary, biomarkers of early responses to CPG 7909 were confirmed, and adding a CpG adjuvant to a vaccine administered twice resulted in increased T cell effects relative to vaccine alone. Changes in early biomarkers correlated with subsequent adaptive humoral immunity but not cellular immunity.

  2. Gorse GJ, et al. "Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine: a randomized, double-blinded, controlled, multicenter trial" [Vaccine 24 (2006) 5950-5959].

    Science.gov (United States)

    Zink, Thomas K

    2007-04-12

    In the study reported by Gorse et al. a unique, educational opportunity was lost. The vaccine and biodefense communities almost experienced the rare chance in a Phase I study to scientifically compare head-to-head an early-stage, investigational recombinant anthrax vaccine (rPA102) with the safe, effective and already FDA-licensed anthrax vaccine, AVA (BioThrax). The authors take a stab at making safety and immunogenicity comparisons between the candidate vaccine and AVA (BioThrax) but the study design and analytical approach makes this inappropriate. Inaccurate and poorly substantiated editorial comments in the paper's introduction compound these methodological problems. The reader is presented with a series of false and misleading statements about AVA (BioThrax). Out-of-date sources are relied upon and these references are offered to the reader as the best evidence available when more current papers with up-to-date information and data exist. Additionally, the conclusions in several original contributions are misrepresented in this paper by Gorse et al. Issues with protocol and bias notwithstanding, the single most compelling observation from this trial could be that the response of those subjects in this study population (n=19) who received AVA on the altered schedule and route of two doses of AVA (BioThrax) delivered intramuscularly (IM) in just 4 weeks mounted a robust immune response. Given the more than 30 year history of the safe and effective use of AVA (BioThrax) as well as the more current data on AVA (BioThrax) a strong case can be made for continued funding to investigate the feasibility of adding another route of delivery (IM) and optimizing the schedule for this already FDA-licensed vaccine.

  3. Randomized, double-blind, active-controlled study evaluating the safety and immunogenicity of three vaccination schedules and two dose levels of AV7909 vaccine for anthrax post-exposure prophylaxis in healthy adults.

    Science.gov (United States)

    Hopkins, Robert J; Kalsi, Gurdyal; Montalvo-Lugo, Victor M; Sharma, Mona; Wu, Yukun; Muse, Derek D; Sheldon, Eric A; Hampel, Frank C; Lemiale, Laurence

    2016-04-19

    AV7909 vaccine being developed for post-exposure prophylaxis of anthrax disease may require fewer vaccinations and reduced amount of antigen to achieve an accelerated immune response over BioThrax(®) (Anthrax Vaccine Adsorbed). A phase 2, randomized, double-blind, BioThrax vacccine-controlled study was conducted to evaluate the safety and immunogenicity of three intramuscular vaccination schedules and two dose levels of AV7909 in 168 healthy adults. Subjects were randomized at a 4:3:2:4:2 ratio to 5 groups: (1) AV7909 on Days 0/14; (2) AV7909 on Days 0/28; (3) AV7909 on Days 0/14/28; (4) half dose AV7909 on Days 0/14/28; and (5) BioThrax vaccine on Days 0/14/28. Vaccinations in all groups were well tolerated. The incidences of adverse events (AEs) were 79% for AV7909 subjects and 65% for BioThrax subjects; 92% of AV7909 subjects and 87% of BioThrax subjects having AEs reported Grade 1-2 AEs. No serious AEs were assessed as potentially vaccine-related, and no AEs of potential autoimmune etiology were reported. There was no discernible pattern indicative of a safety concern across groups in the incidence or severity of reactogenicity events. Groups 2-4 achieved success for the primary endpoint, demonstrated by a lower 95% confidence limit of the percentage of subjects with protective toxin neutralizing antibody NF50 values (≥0.56) to be ≥40% at Day 63. Group 1 marginally missed the criterion (lower bound 95% confidence limit of 39.5%). Immune responses were above this threshold for Groups 1, 3 and 4 at Day 28 and all groups at Day 42. Further study of an AV7909 two-dose schedule given 2 weeks apart is warranted in light of the favorable tolerability profile and immunogenicity response relative to three doses of BioThrax vaccine, as well as preliminary data from nonclinical studies indicating similar immune responses correlate with higher survival for AV7909 than BioThrax vaccine.

  4. Combinations of various CpG motifs cloned into plasmid backbone modulate and enhance protective immunity of viral replicon DNA anthrax vaccines.

    Science.gov (United States)

    Yu, Yun-Zhou; Ma, Yao; Xu, Wen-Hui; Wang, Shuang; Sun, Zhi-Wei

    2015-08-01

    DNA vaccines are generally weak stimulators of the immune system. Fortunately, their efficacy can be improved using a viral replicon vector or by the addition of immunostimulatory CpG motifs, although the design of these engineered DNA vectors requires optimization. Our results clearly suggest that multiple copies of three types of CpG motifs or combinations of various types of CpG motifs cloned into a viral replicon vector backbone with strong immunostimulatory activities on human PBMC are efficient adjuvants for these DNA vaccines to modulate and enhance protective immunity against anthrax, although modifications with these different CpG forms in vivo elicited inconsistent immune response profiles. Modification with more copies of CpG motifs elicited more potent adjuvant effects leading to the generation of enhanced immunity, which indicated a CpG motif dose-dependent enhancement of antigen-specific immune responses. Notably, the enhanced and/or synchronous adjuvant effects were observed in modification with combinations of two different types of CpG motifs, which provides not only a contribution to the knowledge base on the adjuvant activities of CpG motifs combinations but also implications for the rational design of optimal DNA vaccines with combinations of CpG motifs as "built-in" adjuvants. We describe an efficient strategy to design and optimize DNA vaccines by the addition of combined immunostimulatory CpG motifs in a viral replicon DNA plasmid to produce strong immune responses, which indicates that the CpG-modified viral replicon DNA plasmid may be desirable for use as vector of DNA vaccines.

  5. Anthrax Outbreaks in Bangladesh, 2009–2010

    Science.gov (United States)

    Chakraborty, Apurba; Khan, Salah Uddin; Hasnat, Mohammed Abul; Parveen, Shahana; Islam, M. Saiful; Mikolon, Andrea; Chakraborty, Ranjit Kumar; Ahmed, Be-Nazir; Ara, Khorsed; Haider, Najmul; Zaki, Sherif R.; Hoffmaster, Alex R.; Rahman, Mahmudur; Luby, Stephen P.; Hossain, M. Jahangir

    2012-01-01

    During August 2009–October 2010, a multidisciplinary team investigated 14 outbreaks of animal and human anthrax in Bangladesh to identify the etiology, pathway of transmission, and social, behavioral, and cultural factors that led to these outbreaks. The team identified 140 animal cases of anthrax and 273 human cases of cutaneous anthrax. Ninety one percent of persons in whom cutaneous anthrax developed had history of butchering sick animals, handling raw meat, contact with animal skin, or were present at slaughtering sites. Each year, Bacillus anthracis of identical genotypes were isolated from animal and human cases. Inadequate livestock vaccination coverage, lack of awareness of the risk of anthrax transmission from animal to humans, social norms and poverty contributed to these outbreaks. Addressing these challenges and adopting a joint animal and human health approach could contribute to detecting and preventing such outbreaks in the future. PMID:22492157

  6. Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers.

    Science.gov (United States)

    Hopkins, Robert J; Daczkowski, Nancy F; Kaptur, Paulina E; Muse, Derek; Sheldon, Eric; LaForce, Craig; Sari, Suha; Rudge, Thomas L; Bernton, Edward

    2013-06-26

    A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. This Phase 1 study compared the safety and immunogenicity of 2 IM doses (Days 0 and 14) of 4 formulations of AV7909 (AVA plus CPG 7909) with 2 IM doses of BioThrax(®) (Anthrax Vaccine Adsorbed) and 2 IM doses of saline placebo administered on Days 0 and 14. A total of 105 healthy adults 18-50 years of age were randomized to 1 of 6 study groups: BioThrax (0.5 mL), AV7909 Formulation 1 (0.5 mL AVA+0.5mg CPG 7909), AV7909 Formulation 2 (0.5 mL AVA+0.25mg CPG 7909), AV7909 Formulation 3 (0.25 mL AVA+0.5mg CPG 7909), AV7909 Formulation 4 (0.25 mL AVA+0.25mg CPG 7909), or saline placebo (0.5 mL). All randomized subjects received at least 1 vaccination, and 100 subjects completed the trial. After 2 doses, mean peak normalized toxin neutralizing antibody responses (TNA NF50) in the AV7909 groups were higher than in the BioThrax group. Differences among the 4 AV7909 groups were not statistically significant. Subjects who received AV7909 reached peak titers on Day 28 vs. Day 35 in the BioThrax group. The most common adverse events (AEs) in the BioThrax and AV7909 groups assessed as related to vaccination were injection site reactions. Transient lymphopenia was observed after the first dose in each AV7909 group. Frequencies of injection site and systemic reactions recorded by subjects in diaries for 7 days after each injection were highest with AV7909 Formulation 1. No AEs of special interest (autoimmune events) were observed in the study. Further studies of doses and dosing regimens are planned to assess the immunogenicity and reactogenicity of AV7909.

  7. Anthrax as an example of the One Health concept.

    Science.gov (United States)

    Bengis, R G; Frean, J

    2014-08-01

    Anthrax is a peracute, acute or subacute multispecies bacterial infection that occurs on many continents. It is one of the oldest infectious diseases known; the biblical fifth and sixth plagues (Exodus chapters 7 to 9) that affected first livestock and then humans were probably anthrax. From the earliest historical records until development of an effective vaccine midway through the 20th Century, anthrax was one of the foremost causes of uncontrolled mortality in cattle, sheep, goats, horses and pigs, with 'spill over' into humans, worldwide. With the development of the Sterne spore vaccine, a sharp decline in anthrax outbreaks in livestock occurred during the 1930-1980 era. There were successful national vaccination programmes in many countries during this period, complemented by the liberal use of antibiotics and the implementation of quarantine regulations and carcass disposal. However, a resurgence of this disease in livestock has been reported recently in some regions, where complacency and a false sense of security have hindered vaccination programmes. The epidemiology of anthrax involves an environmental component, as well as livestock, wildlife and human components. This makes anthrax an ideal example for discussion in the One Health context. Many outbreaks of anthrax in wildlife are undetected or unreported, owing to surveillance inadequacies and difficulties. Human disease is generally acquired accidentally during outbreaks of anthrax in domestic livestock and wildlife. The exception is deliberate targeting of humans with anthrax in the course of biowarfare or bioterrorism.

  8. The experimental study on safety of the simultaneous immunization of anthrax vaccine and leptospira vaccine%炭疽疫苗和钩端螺旋体疫苗联合接种安全性实验研究

    Institute of Scientific and Technical Information of China (English)

    王亚玉; 邵中军; 李东力; 闫永平

    2012-01-01

    Objective An animal experiment was established to evaluate the safety of the simultaneous vaccination of anthrax vaccine and leptospira vaccine, preparing for the further use in the large population, and to find the optimal dose of simultaneous immunization for the evaluation of safety. Methods 96 mice were randomly divided into 6 groups and the number of male and female was equal. Mice were injected subcutaneously with different doses of vaccine. A combination of 1/10, 1/20, and 1/40 dose of live attenuated anthrax vaccine and 1/5 and 1/3 dose of leptospira vaccine were experimented in 5 groups and 1 group was employed as blank control. Body weight, pathology indices, biochemical indices and spontaneous activity were used to evaluate the safety of immunization. Results Local edema was the main side effect at 48~72 h after simultaneous immunization. 2 mice died in 2 groups (1,1) separately. The white blood cells (WBC) counts increased at the beginning and then became normal after the first simultaneous immunization. This phenomenon could be repeated in the later immunization. There was no significant difference in the other indexes among groups (P>0.05). Conclusions Simultaneous immunization of the optimal doses of live attenuated anthrax vaccine and leptospira vaccine on mice is practicable.%目的 对炭疽疫苗和钩端螺旋体(简称钩体)疫苗进行联合接种动物实验研究,评价联合接种疫苗的安全性,确定最佳实验免疫剂量,为炭疽疫苗和钩体疫苗的人群联合接种提供理论依据.方法 96只实验鼠分层随机分为6组,每组16只,雌雄各半.采用背部皮下接种,取炭疽疫苗1/10、钩体疫苗1/5的人用剂量进行联合接种,同时组合两种疫苗的临近剂量组,即炭疽疫苗1/20、1/40,钩体疫苗1/3的人用剂量进行联合接种,运用体重、血液学指标以及病理组织学等指标对疫苗的安全性进行评价.结果 实验动物接种2种疫苗48~72 h后,部分动物

  9. 9 CFR 311.10 - Anaplasmosis, anthrax, babesiosis, bacillary hemoglobinuria in cattle, blackleg, bluetongue...

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Anaplasmosis, anthrax, babesiosis... DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.10 Anaplasmosis, anthrax... condemned: (1) Anthrax. (2) Blackleg. (3) Unhealed vaccine lesions (vaccinia). (4) Strangles. (5)...

  10. 应用噬菌体进行炭疽疫苗纯菌检查方法的建立%Application of phage for the detection of purity of anthrax vaccine

    Institute of Scientific and Technical Information of China (English)

    魏东; 李恪梅; 王国治

    2012-01-01

    目的 建立应用噬菌体进行炭疽活疫苗纯菌检查的方法,并与现用纯菌检查方法进行比较.方法 使用噬菌体对与炭疽芽孢杆菌分类学上接近以及常见污染细菌进行裂解观察,确定噬菌体特异性.选取具有代表性的可能污染菌定量掺入炭疽疫苗中,制备模拟污染疫苗,进行噬菌体裂解纯菌检查方法的灵敏度研究,同时与现用的直接接种纯菌检查方法进行比较.结果 炭疽噬菌体能特异地裂解炭疽芽孢杆菌,对与炭疽芽孢杆菌分类学上接近以及常见污染细菌无裂解作用.噬菌体裂解法对掺入炭疽疫苗中蜡样芽孢杆菌、枯草芽孢杆菌及大肠埃希菌的检出限均为1 CFU/人份,而现用纯菌检查方法的检出限分别为5、5及50 CFU/人份.结论 噬菌体裂解法检测炭疽活疫苗中污染菌有较好的特异性和灵敏度,该方法的应用对疫苗质量控制具有重要意义.%Objective To develop phage lysis method for the detection of purity of anthrax vaccine and to compare phage lysis method with the routine method .Methods Nine strains of non-Bacillus anthracis were lysed with anthrax phage to evaluate the specificity of phage .The quantified three strains of non-Bacillus anthracis were respectively added into anthrax vaccine to evaluate the sensitivity of phage ,which was compared with the routine method .Results The anthrax phage could lyse Bacillus anthracis and without cross-reaction with other strains of non-Bacillus anthracis .The detection limit of phage lysis method for detection of Bacillus cereus ,Bacillus subtilis and Escherichia coli ,which were added into anthrax vaccine ,were all 1 CFU /dose .The detection limit of routine method for Bacillus cereus ,Bacillus subtilis and Escherichia coli were 5 ,5 and 50 CFU /dose .Conclusion Phage lysis method might be sensitive and specific for detection of purity of anthrax vaccine . This method could be with the potential to be used as a

  11. Recent Developments in Anti-dotes Against Anthrax.

    Science.gov (United States)

    Dhasmana, Neha; Singh, Lalit K; Bhaduri, Asani; Misra, Richa; Singh, Yogendra

    2014-01-01

    The etiologic agent of disease anthrax, Bacillus anthracis, causes recurrent outbreaks among the livestock and intermittent infections in humans across the world. Controlling animal infections by vaccination can minimize the incidence of disease in humans. Prevention of anthrax in occupationally exposed personnel is achieved through vaccination with either live spores or precipitates of culture supernatants from attenuated strains of B. anthracis. However, anthrax vaccination of the large human population is impractical as well as inappropriate. Broad-range antibiotics like amoxicillin, ciprofloxacin, clindamycin, streptomycin, and penicillin G are recommended for the treatment of human anthrax infections, but the threat of antibiotic resistant strains always remains. Moreover, in the absence of any specific symptom (s) during early infection, the diagnosis of anthrax is delayed causing elevated levels of anthrax toxin component which could be fatal. For these reasons, there is a need to develop new antimicrobial agents against virulent B. anthracis to effectively combat this fatal pathogen. Over the last two decades, extensive studies have been carried out to develop specific inhibitors against virulence factors of B. anthracis such as capsule, protective antigen, lethal factor and edema factor. Research has also been focused in developing inhibitors of anthrax toxin receptors (including the use of receptor decoys) and host furin endoproteases which are required for activation of toxin. This review highlights the recent progress made in developing the diverse countermeasures for anthrax infections targeting B. anthracis virulence factors and their counterparts in host.

  12. Factors associated with repeated outbreak of anthrax in Bangladesh: qualitative and quantitative study

    Directory of Open Access Journals (Sweden)

    Jayedul Hassan

    2015-06-01

    Full Text Available Anthrax, caused by Bacillus anthracis is an acute, febrile disease of warm blooded animals including humans. Social norms and poverty in addition to climatic factors such as soil conditions, seasons of year, ambient temperature and rainfall influence the persistence of the B. anthracis and anthrax outbreaks. The present study was designed to reveal the factors influencing the repeated outbreak of anthrax in Bangladesh. Considering the previous outbreaks of anthrax, Sirajganj, Bogra, Kushtia, Tangail and Mymensingh districts of Bangladesh were selected for this study. To elucidate the factors, qualitative data relating to the animal management, knowledge and behavior of the people; and quantitative data relating to soil conditions, ambient temperature and rainfall were acquired, and analyzed critically. Based on the outbreak histories, a year was divided into two seasons, anthrax prone season (May-November and anthrax dry season (December-April. Anthrax spores could be isolated from 11.67% (n=14/120 of the soil samples collected from the study areas. The present study revealed that poor knowledge, lack of awareness, improper carcass disposal, inadequate vaccination, high Ca content and moisture in the soil along with high ambient temperature and rainfall during the anthrax prone season were the possible influencing factors of repeated outbreaks of anthrax in the study areas. Intensive propaganda to create public awareness of anthrax together with proper vaccination may reduce anthrax outbreaks in Bangladesh.

  13. Inhalational anthrax (Ames aerosol) in naive and vaccinated New Zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia.

    OpenAIRE

    Bradford eGutting; Tonya L Nichols; Channel, Stephen R.; Gearhart, Jeffery M.; Andrews, George A.; Berger, Alan E.; Mackie, Ryan S.; Brent J Watson; Taft, Sarah C.; Overheim, Katie A.; Robert L Sherwood

    2012-01-01

    There is a need to better understand inhalational anthrax in relevant animal models. This understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. The aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (>100LD50) of Bacillus anthracis (Ames) spores immediately following exposure through 36 hours. The primary goal of collecting the data w...

  14. 76 FR 53480 - Prospective Grant of Exclusive License: Conjugate Vaccines Against B. anthracis

    Science.gov (United States)

    2011-08-26

    ... HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Conjugate Vaccines... factor'' (EF). Although production of an efficient anthrax vaccine is an ultimate goal, the benefits of... therapy of B. anthracis (anthrax) infection by immunization with conjugate vaccines against anthrax...

  15. Human anthrax outbreak associated with livestock exposure: Georgia, 2012.

    Science.gov (United States)

    Navdarashvili, A; Doker, T J; Geleishvili, M; Haberling, D L; Kharod, G A; Rush, T H; Maes, E; Zakhashvili, K; Imnadze, P; Bower, W A; Walke, H T; Shadomy, S V

    2016-01-01

    Human anthrax cases reported in the country of Georgia increased 75% from 2011 (n = 81) to 2012 (n = 142). This increase prompted a case-control investigation using 67 culture- or PCR-confirmed cases and 134 controls matched by residence and gender to investigate risk factor(s) for infection during the month before case onset. Independent predictors most strongly associated with disease in the multivariable modelling were slaughtering animals [odds ratio (OR) 7·3, 95% confidence interval (CI) 2·9-18·1, P 1 km; 15 (12%) of 125 had sick livestock; and 11 (9%) of 128 respondents reported finding dead livestock. We recommend joint public health and veterinary anthrax case investigations to identify areas of increased risk for livestock anthrax outbreaks, annual anthrax vaccination of livestock in those areas, and public awareness education.

  16. Anthrax undervalued zoonosis

    OpenAIRE

    2010-01-01

    Abstract Anthrax is a non-contagious disease, known since ancient times but it became a matter of global public interest after the bioterrorist attacks in the U.S.A. during the autumn of 2001. The concern of politicians and civil authorities everywhere towards this emergency necessitated a significant research effort and the prevention of new bioterrorist acts. But anthrax is primarily a disease that affects livestock and wildlife; its distribution is worldwide; and it can represen...

  17. Public health and bioterrorism: renewed threat of anthrax and smallpox.

    Science.gov (United States)

    Wallin, Arūne; Luksiene, Zivile; Zagminas, Kestutis; Surkiene, Gene

    2007-01-01

    Bioterrorism is one of the main public health categorical domains. According to sociological analytics, in postmodern society terrorism is one of the real threats of the 21st century. While rare, the use of biological weapons has a long history. Recently, anthrax has been evaluated as one of the most dangerous biological weapons. Naturally occurring anthrax in humans is a disease acquired from contact with anthrax-infected animals or anthrax-contaminated animal products. Usually anthrax infection occurs in humans by three major routes: inhalational, cutaneous, and gastrointestinal. Inhalational anthrax is expected to account for most serious morbidity and most mortality. The clinical presentation of inhalation anthrax has been described as a two-stage illness. Many factors contribute to the pathogenesis of Bacillus anthracis. Antibiotics, anthrax globulin, corticosteroids, mechanical ventilation, vaccine are possible tools of therapy. Smallpox existed in two forms: variola major, which accounted for most morbidity and mortality, and a milder form, variola minor. Smallpox spreads from person to person primarily by droplet nuclei or aerosols expelled from the oropharynx of infected persons and by direct contact. In the event of limited outbreak with few cases, patients should be admitted to the hospital and confined to rooms that are under negative pressure and equipped with high-efficiency particulate air filtration. In larger outbreaks, home isolation and care should be the objective for most patients. Progress in detection, suitable vaccines, postexposure prophylaxis, infection control, and decontamination might be serious tools in fight against the most powerful biological weapon. To assure that the public health and healthcare system can respond to emergencies, the government should direct resources to strengthen the emergency-response system, create medication stockpiles, and improve the public health infrastructure.

  18. 炭疽PA和芽孢双组分候选疫苗免疫豚鼠的免疫学初步评价%Preliminary immunological evaluation of a two-component anthrax candidate vaccine comprised of PA and Spores in Guinea pigs

    Institute of Scientific and Technical Information of China (English)

    卢锦标; 魏东; 王国治

    2013-01-01

    Objective To evaluate the immune response in guinea pigs vaccinated with a two-component anthrax candidate vaccine comprised of PA and spores.Methods Guinea pigs were randomly divided into five groups and vaccinated with high-dose,medium-dose and low-dose candidate vaccine,anthrax live vaccine and normal saline,respectively.Serum antibody,XTT cell proliferation and DTH were detected at different times after the last vaccination.Results Antibody detection indicated the two-component anthrax candidate vaccine induced strong humoral immune response.XTT proliferation test showed specific proliferation of peripheral blood lymphocytes was not obvious.However,in all candidate vaccine groups DTH conversion rate to rPA was 100% in 24 h.Conclusion The two-component anthrax candidate vaccine could induce both humoral and cellular immune response in guinea pigs.%目的 对豚鼠免疫重组PA抗原和甲醛灭活芽孢组成的炭疽候选疫苗,评价其免疫效果.方法 将豚鼠随机分成5个实验组,分别免疫高、中、低剂量候选疫苗、炭疽活疫苗或生理盐水;免疫后不同时间点采血进行抗体检测、XTT法淋巴细胞增殖检测以及皮肤迟发型超敏反应检测.结果 抗体检测结果显示,双组分炭疽候选疫苗能诱导较强的体液免疫应答;XTT细胞增殖结果显示,外周血淋巴细胞特异性增殖不明显,但所有候选疫苗组针对rPA DTH阳转率24 h后均为100%.结论 双组分炭疽候选疫苗能诱导豚鼠产生体液免疫和细胞免疫应答.

  19. Risk practices for animal and human anthrax in Bangladesh: an exploratory study

    Science.gov (United States)

    Islam, Md. Saiful; Hossain, M. Jahangir; Mikolon, Andrea; Parveen, Shahana; Khan, M. Salah Uddin; Haider, Najmul; Chakraborty, Apurba; Titu, Abu Mohammad Naser; Rahman, M. Waliur; Sazzad, Hossain M. S.; Rahman, Mahmudur; Gurley, Emily S.; Luby, Stephen P.

    2013-01-01

    Introduction From August 2009 to October 2010, International Centre for Diarrheal Disease Research, Bangladesh and the Institute of Epidemiology, Disease Control and Research together investigated 14 outbreaks of anthrax which included 140 animal and 273 human cases in 14 anthrax-affected villages. Our investigation objectives were to explore the context in which these outbreaks occurred, including livestock rearing practices, human handling of sick and dead animals, and the anthrax vaccination program. Methods Field anthropologists used qualitative data-collection tools, including 15 hours of unstructured observations, 11 key informant interviews, 32 open-ended interviews, and 6 group discussions in 5 anthrax-affected villages. Results Each cattle owner in the affected communities raised a median of six ruminants on their household premises. The ruminants were often grazed in pastures and fed supplementary rice straw, green grass, water hyacinth, rice husk, wheat bran, and oil cake; lactating cows were given dicalcium phosphate. Cattle represented a major financial investment. Since Islamic law forbids eating animals that die from natural causes, when anthrax-infected cattle were moribund, farmers often slaughtered them on the household premises while they were still alive so that the meat could be eaten. Farmers ate the meat and sold it to neighbors. Skinners removed and sold the hides from discarded carcasses. Farmers discarded the carcasses and slaughtering waste into ditches, bodies of water, or open fields. Cattle in the affected communities did not receive routine anthrax vaccine due to low production, poor distribution, and limited staffing for vaccination. Conclusion Slaughtering anthrax-infected animals and disposing of butchering waste and carcasses in environments where ruminants live and graze, combined with limited vaccination, provided a context that permitted repeated anthrax outbreaks in animals and humans. Because of strong financial incentives

  20. Risk practices for animal and human anthrax in Bangladesh: an exploratory study

    Directory of Open Access Journals (Sweden)

    Md. Saiful Islam

    2013-11-01

    Full Text Available Introduction: From August 2009 to October 2010, International Centre for Diarrheal Disease Research, Bangladesh and the Institute of Epidemiology, Disease Control and Research together investigated 14 outbreaks of anthrax which included 140 animal and 273 human cases in 14 anthrax-affected villages. Our investigation objectives were to explore the context in which these outbreaks occurred, including livestock rearing practices, human handling of sick and dead animals, and the anthrax vaccination program. Methods: Field anthropologists used qualitative data-collection tools, including 15 hours of unstructured observations, 11 key informant interviews, 32 open-ended interviews, and 6 group discussions in 5 anthrax-affected villages. Results: Each cattle owner in the affected communities raised a median of six ruminants on their household premises. The ruminants were often grazed in pastures and fed supplementary rice straw, green grass, water hyacinth, rice husk, wheat bran, and oil cake; lactating cows were given dicalcium phosphate. Cattle represented a major financial investment. Since Islamic law forbids eating animals that die from natural causes, when anthrax-infected cattle were moribund, farmers often slaughtered them on the household premises while they were still alive so that the meat could be eaten. Farmers ate the meat and sold it to neighbors. Skinners removed and sold the hides from discarded carcasses. Farmers discarded the carcasses and slaughtering waste into ditches, bodies of water, or open fields. Cattle in the affected communities did not receive routine anthrax vaccine due to low production, poor distribution, and limited staffing for vaccination. Conclusion: Slaughtering anthrax-infected animals and disposing of butchering waste and carcasses in environments where ruminants live and graze, combined with limited vaccination, provided a context that permitted repeated anthrax outbreaks in animals and humans. Because of strong

  1. Investigation of Anthrax Cases in North-East China, 2010-2014.

    Science.gov (United States)

    Zhou, Wei; Sun, Yang; Zhu, Lingwei; Zhou, Bo; Liu, Jun; Ji, Xue; Wang, Xiaofeng; Wang, Nan; Gu, Guibo; Feng, Shuzhang; Qian, Jun; Guo, Xuejun

    2015-01-01

    We determined the genotypes of seven Bacillus anthracis strains that were recovered from nine anthrax outbreaks in North-East China from 2010 to 2014, and two approved vaccine strains that are currently in use in China. The causes of these cases were partly due to local farmers being unaware of the presence of anthrax, and butchers with open wounds having direct contact with anthrax-contaminated meat products. The genotype of five of the seven recovered strains was A.Br.001/002 sub-lineage, which was concordant with previously published research. The remaining two cases belongs to the A.Br.Ames sub-lineage. Both of these strains displayed an identical SNR pattern, which was the first time that this genotype was identified in North-East China. Strengthening education in remote villages of rural China is an important activity aimed at fostering attempts to prevent and control anthrax. The genotype of the vaccine strain Anthrax Spore Vaccine No.II was A.Br.008/009 and A.Br.001/002 for the vaccine strain Anthrax Spore Vaccine Non-capsulated. Further studies of their characteristics are clearly warranted.

  2. Anthrax (Lecture Aids) - USSR .

    Science.gov (United States)

    1961-08-14

    utions (phenol, lysol , etc.) and dies at a temperature of 60-70 C. As opposed to the vegetative form, the anthrax spore is extremely resistant to...external influences. Ord- inary disinfectant solutions (corrosive sublimate, carbolic acid, lysol ) are not used, since they have little effect on

  3. An Alternative Approach to Combination Vaccines: Intradermal Administration of Isolated Components for Control of Anthrax, Botulism, Plague and Staphylococcal Toxic Shock

    Science.gov (United States)

    2008-09-03

    retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from...shock were biocompatible in vivo, retained potent antibody responses, and were well tolerated by rhesus macaques. Vaccinated primates were completely...foodstuff into the trachea and lungs due to dysphagia secondary to cranial nerve paralysis after exposure to the toxin. White blood cell counts of the

  4. Heroin-associated anthrax with minimal morbidity.

    Science.gov (United States)

    Black, Heather; Chapman, Ann; Inverarity, Donald; Sinha, Satyajit

    2017-03-08

    In 2010, during an outbreak of anthrax affecting people who inject drugs, a heroin user aged 37 years presented with soft tissue infection. He subsequently was found to have anthrax. We describe his management and the difficulty in distinguishing anthrax from non-anthrax lesions. His full recovery, despite an overall mortality of 30% for injectional anthrax, demonstrates that some heroin-related anthrax cases can be managed predominately with oral antibiotics and minimal surgical intervention.

  5. Anthrax lethal and edema toxins in anthrax pathogenesis.

    Science.gov (United States)

    Liu, Shihui; Moayeri, Mahtab; Leppla, Stephen H

    2014-06-01

    The pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. B. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the USA. The exotoxins secreted by B. anthracis use capillary morphogenesis protein 2 (CMG2) as the major toxin receptor and play essential roles in pathogenesis during the entire course of the disease. This review focuses on the activities of anthrax toxins and their roles in initial and late stages of anthrax infection.

  6. Methods for neutralizing anthrax or anthrax spores

    Science.gov (United States)

    Sloan, Mark A; Vivekandanda, Jeevalatha; Holwitt, Eric A; Kiel, Johnathan L

    2013-02-26

    The present invention concerns methods, compositions and apparatus for neutralizing bioagents, wherein bioagents comprise biowarfare agents, biohazardous agents, biological agents and/or infectious agents. The methods comprise exposing the bioagent to an organic semiconductor and exposing the bioagent and organic semiconductor to a source of energy. Although any source of energy is contemplated, in some embodiments the energy comprises visible light, ultraviolet, infrared, radiofrequency, microwave, laser radiation, pulsed corona discharge or electron beam radiation. Exemplary organic semiconductors include DAT and DALM. In certain embodiments, the organic semiconductor may be attached to one or more binding moieties, such as an antibody, antibody fragment, or nucleic acid ligand. Preferably, the binding moiety has a binding affinity for one or more bioagents to be neutralized. Other embodiments concern an apparatus comprising an organic semiconductor and an energy source. In preferred embodiments, the methods, compositions and apparatus are used for neutralizing anthrax spores.

  7. The pattern of anthrax cases on livestock in West Nusa Tenggara Province

    Directory of Open Access Journals (Sweden)

    Enymartindah

    1998-03-01

    Full Text Available A retrospective study on anthrax in endemic area was carried out from 1984 to 1994 in West Nusa Tenggara Province (NTB to uncover the occurrence of anthrax and the pattern of the disease in livestock. Data of anthrax incidence had been compiled for the 11 years from Animal Health Section and Type B Laboratory of the Livestock Service Office, NTB Province in Mataram. This was done to get the information about locations and times when the cases occurred, and the vaccination status of livestock in the anthrax area. The pattern of anthrax in livestock was analyzed by using time series analysis, and the long term trend was then illustrated by linier regression . During the years, anthrax cases in livestock were reported high in Sumbawa island, while the cases in Lombok island were relatively low. There were no anthrax cases reported from East Lombok District . The long term trend of anthrax occurrence in livestock from 1984 to 1994 tended to decrease (Y= 6,04 - 0,0162 X.

  8. Pediatric anthrax clinical management.

    Science.gov (United States)

    Bradley, John S; Peacock, Georgina; Krug, Steven E; Bower, William A; Cohn, Amanda C; Meaney-Delman, Dana; Pavia, Andrew T

    2014-05-01

    Anthrax is a zoonotic disease caused by Bacillus anthracis, which has multiple routes of infection in humans, manifesting in different initial presentations of disease. Because B anthracis has the potential to be used as a biological weapon and can rapidly progress to systemic anthrax with high mortality in those who are exposed and untreated, clinical guidance that can be quickly implemented must be in place before any intentional release of the agent. This document provides clinical guidance for the prophylaxis and treatment of neonates, infants, children, adolescents, and young adults up to the age of 21 (referred to as "children") in the event of a deliberate B anthracis release and offers guidance in areas where the unique characteristics of children dictate a different clinical recommendation from adults.

  9. Anthrax Spores under a microscope

    Science.gov (United States)

    2003-01-01

    Anthrax spores are inactive forms of Bacillus anthracis. They can survive for decades inside a spore's tough protective coating; they become active when inhaled by humans. A result of NASA- and industry-sponsored research to develop small greenhouses for space research is the unique AiroCide TiO2 system that kills anthrax spores and other pathogens.

  10. [Anthrax due to deliberate infection

    NARCIS (Netherlands)

    Dissel, J.T. van; Kullberg, B.J.; Berg, P.C. van den; Steenbergen, J.E. van

    2001-01-01

    Anthrax is a zoonosis which is particularly prevalent in cattle, goats and sheep and is caused by Bacillus anthracis, a Gram-positive spore forming aerobic microorganism. The endospores can survive outside of the body for many decades. The natural form of anthrax has a cutaneous, pulmonary and intes

  11. Three eyelid localized cutaneous anthrax cases.

    Science.gov (United States)

    Esmer, Oktay; Karadag, Remzi; Bilgili, Serap Gunes; Gultepe, Bilge; Bayramlar, Huseyin; Karadag, Ayse Serap

    2014-12-01

    Anthrax is primarily seen in the developing countries, but it can be a worldwide medical concern due to bioterrorism threats. Palpebral anthrax is a rare form of cutaneous anthrax. Untreated cutaneous anthrax can be lethal. Patients with palpebral anthrax can develop complications including cicatrisation and ectropion. Thus, anthrax should be considered in differential diagnosis for patients presenting with preseptal cellulitis in high-risk regions. Herein, we report three anthrax cases (with different age) involving eyelids that were cured without any complications due to early diagnosis and treatment.

  12. Inhalation Anthrax (Ames aerosol) in Naive and Vaccinated New Zealand Rabbits: Characterizing the Spread of Bacteria from Lung Deposition to Bacteremia

    Science.gov (United States)

    2012-06-28

    strain bacteria (pXO1+ and pXO2+) were obtained from C. Rick Lyons of the University of New Mexico . Spores were grown in trypticase soy broth...CLEARANCE FROM THE AIRWAYS The number of bacteria in the airways over time was deter- mined by dilution plate analysis of BAL using methods identical...deter- mined (Table 4). Bacteria first appeared at 12 h in the TBLN from sham-vaccinated animals where CFU were detected in three of five animals (44 ± 19

  13. Anthrax receptors position the spindle.

    Science.gov (United States)

    Minc, Nicolas; Piel, Matthieu

    2013-01-01

    Spindle orientation plays a pivotal role in tissue morphogenesis. An asymmetric anthrax receptor cap is revealed to promote activation of a formin to orient the spindle along the planar cell polarity (PCP) axis in zebrafish dorsal epiblast cells.

  14. Evidence of local persistence of human anthrax in the country of georgia associated with environmental and anthropogenic factors.

    Directory of Open Access Journals (Sweden)

    Ian T Kracalik

    Full Text Available BACKGROUND: Anthrax is a soil-borne disease caused by the bacterium Bacillus anthracis and is considered a neglected zoonosis. In the country of Georgia, recent reports have indicated an increase in the incidence of human anthrax. Identifying sub-national areas of increased risk may help direct appropriate public health control measures. The purpose of this study was to evaluate the spatial distribution of human anthrax and identify environmental/anthropogenic factors associated with persistent clusters. METHODS/FINDINGS: A database of human cutaneous anthrax in Georgia during the period 2000-2009 was constructed using a geographic information system (GIS with case data recorded to the community location. The spatial scan statistic was used to identify persistence of human cutaneous anthrax. Risk factors related to clusters of persistence were modeled using a multivariate logistic regression. Areas of persistence were identified in the southeastern part of the country. Results indicated that the persistence of human cutaneous anthrax showed a strong positive association with soil pH and urban areas. CONCLUSIONS/SIGNIFICANCE: Anthrax represents a persistent threat to public and veterinary health in Georgia. The findings here showed that the local level heterogeneity in the persistence of human cutaneous anthrax necessitates directed interventions to mitigate the disease. High risk areas identified in this study can be targeted for public health control measures such as farmer education and livestock vaccination campaigns.

  15. Evidence of Local Persistence of Human Anthrax in the Country of Georgia Associated with Environmental and Anthropogenic Factors

    Science.gov (United States)

    Kracalik, Ian T.; Malania, Lile; Tsertsvadze, Nikoloz; Manvelyan, Julietta; Bakanidze, Lela; Imnadze, Paata; Tsanava, Shota; Blackburn, Jason K.

    2013-01-01

    Background Anthrax is a soil-borne disease caused by the bacterium Bacillus anthracis and is considered a neglected zoonosis. In the country of Georgia, recent reports have indicated an increase in the incidence of human anthrax. Identifying sub-national areas of increased risk may help direct appropriate public health control measures. The purpose of this study was to evaluate the spatial distribution of human anthrax and identify environmental/anthropogenic factors associated with persistent clusters. Methods/Findings A database of human cutaneous anthrax in Georgia during the period 2000–2009 was constructed using a geographic information system (GIS) with case data recorded to the community location. The spatial scan statistic was used to identify persistence of human cutaneous anthrax. Risk factors related to clusters of persistence were modeled using a multivariate logistic regression. Areas of persistence were identified in the southeastern part of the country. Results indicated that the persistence of human cutaneous anthrax showed a strong positive association with soil pH and urban areas. Conclusions/Significance Anthrax represents a persistent threat to public and veterinary health in Georgia. The findings here showed that the local level heterogeneity in the persistence of human cutaneous anthrax necessitates directed interventions to mitigate the disease. High risk areas identified in this study can be targeted for public health control measures such as farmer education and livestock vaccination campaigns. PMID:24040426

  16. Cutaneous anthrax cases leading compartment syndrome

    Directory of Open Access Journals (Sweden)

    Emine Parlak

    2013-12-01

    Full Text Available Bacillus anthracis is the causative agent of anthrax. Anthrax is a zoonotic disease with three clinical forms. Clinical forms are skin, gastrointestinal and inhalational anthrax. Cutaneous anthrax is 95% of the cases. Cutaneous anthrax frequently defines itself. Clinical presentation of anthrax may be severe and complicated in some cases. There may seem complications like meningitis, septic shock and compartment syndrome. Compartment Syndrome is a rare complication of cutaneous anthrax and it is life threatening. Physicians working in the endemic area should be aware of this form. In this study, three cases were shown which developed compartment syndrome following cutaneous anthrax. J Microbiol Infect Dis 2013;3(4: 214-217

  17. Anthrax: A Guide for Biology Teachers.

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

    Presents facts about anthrax so that biology teachers can communicate them to others. Defines anthrax and the nature of bacterial spores. Discusses transmission and clinical presentation as well as prevention, diagnosis, and treatment. Explores the use of anthrax as a biological warfare agent. (Contains 27 references.) (DDR)

  18. Anthrax - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Anthrax URL of this page: https://medlineplus.gov/languages/anthrax.html Other topics A-Z A B C ... V W XYZ List of All Topics All Anthrax - Multiple Languages To use the sharing features on ...

  19. Investigation of inhalation anthrax case, United States.

    Science.gov (United States)

    Griffith, Jayne; Blaney, David; Shadomy, Sean; Lehman, Mark; Pesik, Nicki; Tostenson, Samantha; Delaney, Lisa; Tiller, Rebekah; DeVries, Aaron; Gomez, Thomas; Sullivan, Maureen; Blackmore, Carina; Stanek, Danielle; Lynfield, Ruth

    2014-02-01

    Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States.

  20. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  1. Airing Out Anthrax

    Science.gov (United States)

    2002-01-01

    The AiroCide TiO2 is an air-purifier that kills 93.3 percent of airborne pathogens that pass through it, including Bacillus anthraci, more commonly known as anthrax. It is essentially a spinoff of KES Science & Technology, Inc.'s Bio-KES system, a highly effective device used by the produce industry for ethylene gas removal to aid in preserving the freshness of fruits, vegetables, and flowers. The TiO2-based ethylene removal technology that is incorporated into the company's AiroCide TiO2 and Bio-KES products was first integrated into a pair of plant-growth chambers known as ASTROCULTURE(TM) and ADVANCED ASTROCULTURE(TM). Both chambers have housed commercial plant growth experiments in space on either the Space Shuttle or the International Space Station. The AiroCide TiO2 also has a proven record of destroying 98 percent of other airborne pathogens, such as microscopic dust mites, molds, and fungi. Moreover, the device is a verified killer of Influenza A (flu), E. coli, Staphylococcus aureas, Streptococcus pyogenes, and Mycoplasma pneumoniae, among many other harmful viruses.

  2. Existing antibacterial vaccines.

    Science.gov (United States)

    Mendoza, Natalia; Ravanfar, Parisa; Satyaprakash, Anita; Satyaprakah, Anita; Pillai, Sivaprabha; Creed, Rosella

    2009-01-01

    There are countless bacterial pathogens that cause disease in humans. Many of these bacterial infections not only cause significant morbidity and mortality in the human population but also cause a significant economic impact on society. Vaccines allow for reduction and potential eradication of such diseases. This article will review the currently approved antibacterial vaccines, which are vaccines for pertussis, tetanus, diphtheria, meningococcus, pneumococcus, Haemophilus influenza, cholera, typhoid, and anthrax.

  3. Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009 (Morbidity and Mortality Weekly Report. Volume 59, Number RR-6, July 23, 2010)

    Science.gov (United States)

    2010-07-23

    Streptococcus pyogenes in children. Antimicrob Agents Chemother 2008;52:2512–20. 220. Rollag Jr H, Midtvedt T, Wetterhus S. Serum levels of penicillin V...contaminated animal products or an infected animal (28). Agricultural cases of anthrax occur among persons who have direct contact with infected sick ...limited to support a regimen of ឬ days. Oral ciprofloxacin, oral doxycycline, and parenteral (IM) penicillin G procaine have been shown to be

  4. Anthrax - Pasteur to the Present

    Science.gov (United States)

    1987-01-01

    Hausler, Jr., H. J. Shadomy (ed.l, ASM Manual of Clinical Microbiology , 4th Edition , American Society for Microbiology , Washington, D.C. 4. Dutz, W. and E...Harrison, L. 14ý et at. 1986. Application of an electro- phoretic iAaunotransblot method for the serologic diagnosis of anthrax. 26th Inttrsci. Conf

  5. Designing Inhibitors of Anthrax Toxin

    Science.gov (United States)

    Nestorovich, Ekaterina M.; Bezrukov, Sergey M.

    2014-01-01

    Introduction Present-day rational drug design approaches are based on exploiting unique features of the target biomolecules, small- or macromolecule drug candidates, and physical forces that govern their interactions. The 2013 Nobel Prize in chemistry awarded “for the development of multiscale models for complex chemical systems” once again demonstrated the importance of the tailored drug discovery that reduces the role of the trial and error approach to a minimum. The “rational drug design” term is rather comprehensive as it includes all contemporary methods of drug discovery where serendipity and screening are substituted by the information-guided search for new and existing compounds. Successful implementation of these innovative drug discovery approaches is inevitably preceded by learning the physics, chemistry, and physiology of functioning of biological structures under normal and pathological conditions. Areas covered This article provides an overview of the recent rational drug design approaches to discover inhibitors of anthrax toxin. Some of the examples include small-molecule and peptide-based post-exposure therapeutic agents as well as several polyvalent compounds. The review also directs the reader to the vast literature on the recognized advances and future possibilities in the field. Expert opinion Existing options to combat anthrax toxin lethality are limited. With the only anthrax toxin inhibiting therapy (PA-targeting with a monoclonal antibody, raxibacumab) approved to treat inhalational anthrax, in our view, the situation is still insecure. The FDA’s animal rule for drug approval, which clears compounds without validated efficacy studies on humans, creates a high level of uncertainty, especially when a well-characterized animal model does not exist. Besides, unlike PA, which is known to be unstable, LF remains active in cells and in animal tissues for days. Therefore, the effectiveness of the post-exposure treatment of the individuals

  6. Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

    Science.gov (United States)

    Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Merkel, Tod J

    2014-04-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

  7. Methods of Eradicating Anthrax - USSR -

    Science.gov (United States)

    2007-11-02

    case of other zoonoses ( brucellosis , rabies, foot- and-mouth disease). Such frequent cases of infection of persons from sick animals indicates an...the diagnosis of anthrax in man« As shown by an analysis of available data, the- overwhelming majority of cases in man have not been confirmed by...bacteriological examination and the diagnosis has been based on clinical and epidemiological or simply clinical data» If the measures indicated are

  8. Oculocutaneous anthrax: detection and treatment

    Directory of Open Access Journals (Sweden)

    Sarada David

    2010-07-01

    Full Text Available Sarada David1, Jayanthi Peter1, Renu Raju2, P Padmaja2, Promila Mohanraj21Department of Ophthalmology, Schell Eye Hospital, Christian Medical College Hospital, Vellore, India; 2Department of Microbiology, Christian Medical College Hospital, Vellore, IndiaAbstract: Anthrax, a zoonotic disease that primarily affects herbivores, has received recent attention as a potential agent of bioterrorism. We report a patient who presented with a 4-day history of pain, watering and difficulty in opening the left upper and lower eyelids, and fever. Clinical examination revealed brawny nonpitting edema with serosanguinous discharge. The history of the death of his sheep 1 week prior to the illness provided the clue to the diagnosis. Although standard cultures of the blood and the serous fluid from the lesion were negative, probably as a result of prior treatment, the diagnosis of cutaneous anthrax was made by a polymerase chain reaction (PCR test of the serous fluid. Serial photographs demonstrating resolution of the lesion with appropriate antibiotic therapy are presented.Keywords: anthrax, polymerase chain reaction, treatment

  9. Neutron-based sterilization of anthrax contamination.

    Science.gov (United States)

    Liu, Bin; Wang, Qingfei

    2006-05-01

    With the anthrax threat becoming a reality, it is very important to have an effective way to sterilize areas contaminated by anthrax. Anthrax spores are the dormant form of the anthrax bacteria. They can germinate in tissues, producing new bacteria that release lethal toxins. Neutrons can be a powerful tool in our defense against anthrax contamination. Neutrons are elementary particles that have no charge, which allows them to be very penetrating, killing the anthrax spores on the surface and inside the containers. So neutrons have an advantage over other forms of radiation if deep penetration is required to kill biological organisms. A Cf neutron source allows for a low cost method of decontamination. It emits most neutrons in the 100 keV to 2 MeV energy regions, and a neutron in this energy region is 20 times more deadly than electrons or gamma rays in killing anthrax spores. If we just consider the first neutron collision with anthrax spores and that all the anthrax spores will not survive at the dose level above 2.0 x 10 Gy, our calculations show that a 0.5-g Cf neutron source within 20 min can generate 1.11 x 10 m fluence neutrons, which is good enough to kill the anthrax spores on the sample. An experimental confirmation of the above results may prove that to achieve 1.11 x 10 m fluence neutrons on the anthrax spore sample, the neutron irradiation time may be reduced dramatically or the Cf neutron source reduced to 0.1 g level or even less. The aim of this paper is to evaluate a feasible way to sterilize the anthrax contamination by using a Cf neutron source. Presently, we are mainly concentrating on the theoretical estimation of neutron fluence to see if the Cf neutron source can deliver enough neutron irradiation dose to kill the anthrax spores. Our future work will focus on experimental confirmation and Monte Carlo simulation by using Geant4 or MCNP codes. At that time, we will consider the effects of the real experimental setup, the shielding materials

  10. Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection.

    Directory of Open Access Journals (Sweden)

    Matthew D Reed

    Full Text Available Protective antigen (PA, one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax. Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions. Mutant derivatives of the protective antigen that will not form the anthrax toxins have been described. We have cloned and expressed both mutant (PA SNKE167-ΔFF-315-E308D and native PA molecules recombinantly and purified them. In this study, both the mutant and native PA molecules, formulated with alum (Alhydrogel, elicited high titers of anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both mutant and native PA vaccine preparations protected rabbits from lethal, aerosolized, B. anthracis spore challenge subsequent to two immunizations at doses of less than 1 μg.

  11. Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection.

    Science.gov (United States)

    Reed, Matthew D; Wilder, Julie A; Mega, William M; Hutt, Julie A; Kuehl, Philip J; Valderas, Michelle W; Chew, Lawrence L; Liang, Bertrand C; Squires, Charles H

    2015-01-01

    Protective antigen (PA), one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax). Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively) supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions. Mutant derivatives of the protective antigen that will not form the anthrax toxins have been described. We have cloned and expressed both mutant (PA SNKE167-ΔFF-315-E308D) and native PA molecules recombinantly and purified them. In this study, both the mutant and native PA molecules, formulated with alum (Alhydrogel), elicited high titers of anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both mutant and native PA vaccine preparations protected rabbits from lethal, aerosolized, B. anthracis spore challenge subsequent to two immunizations at doses of less than 1 μg.

  12. Treatment of Anthrax Disease Frequently Asked Questions

    Energy Technology Data Exchange (ETDEWEB)

    Judd, Kathleen S.; Young, Joan E.; Lesperance, Ann M.; Malone, John D.

    2010-05-14

    This document provides a summary of Frequently Asked Questions (FAQs) on the treatment of anthrax disease caused by a wide-area release of Bacillus anthracis spores as an act bioterrorism. These FAQs are intended to provide the public health and medical community, as well as others, with guidance and communications to support the response and long-term recovery from an anthrax event.

  13. Anthrax Prank Against Teacher Backfires

    Institute of Scientific and Technical Information of China (English)

    梅德名

    2001-01-01

    911事件在美国人心中投下的巨大阴影尚未消失,炭疽热(anthrax)恐怖接踵而至!我国的有关部门已经发布行政命令:禁止邮寄白色粉末。值此“杯弓蛇影”之际,美国佛罗里达州的一位中学生居然“顶风行事”:上课前在讲台上撒了白色粉末……

  14. Select human anthrax protective antigen (PA) epitope-specific antibodies provide protection from lethal toxin challenge

    Science.gov (United States)

    Crowe, Sherry R.; Ash, Linda L.; Engler, Renata J. M.; Ballard, Jimmy D.; Harley, John B.; Farris, A. Darise; James, Judith A.

    2010-01-01

    Bacillus anthracis remains a serious bioterrorism concern, and the currently licensed vaccine remains an incomplete solution for population protection from inhalation anthrax and has been associated with concerns regarding efficacy and safety. Thus, understanding how to generate long lasting protective immunity with reduced immunizations or providing protection through post exposure immunotherapeutics are long sought goals. Through evaluation of a large military cohort, we characterized the levels of antibodies against protective antigen and found that over half of anthrax vaccinees had low levels of in vitro toxin neutralization capacity in their sera. Using solid phase epitope mapping and confirmatory assays, we identified several neutralization-associated humoral epitopes and demonstrated that select anti-peptide responses mediated protection in vitro. Finally, passively transferred antibodies specific for select epitopes provided protection in an in vivo lethal toxin mouse model. Identification of these antigenic regions has important implications for vaccine design and the development of directed immunotherapeutics. PMID:20533877

  15. Human Cutaneous Anthrax, the East Anatolian Region of Turkey 2008-2014.

    Science.gov (United States)

    Parlak, Emine; Parlak, Mehmet

    2016-01-01

    Anthrax is a zoonotic infectious disease caused by Bacillus anthracis. While anthrax is rare in developed countries, it is endemic in Turkey. The names of the different forms of the disease refer to the manner of entry of the spores into the body-cutaneous, gastrointestinal, inhalation, and injection. The purpose of this study was to evaluate the clinical characteristics, epidemiological history, treatment, and outcomes of patients with anthrax. Eighty-two cases of anthrax hospitalized at Atatürk University Faculty of Medicine Department of Infectious Diseases and Clinical Microbiology in 2008-2014 were examined retrospectively. Gender, age, occupation, year, history, clinical characteristics, character of lesions, length of hospitalization, and outcomes were recorded. Thirty (36.6%) patients were female and 52 (63.4%) patients were male; ages were 18-69 and mean age was 43.77 ± 13.05. The mean incubation period was 4.79 ± 3.76 days. Cases were largely identified in August (41.5%) and September (25.6%). Sixty-nine (84.1%) of the 82 patients had been given antibiotics before presentation. Lesions were most common on the fingers and arms. The most common occupational groups were housewives (36.6%) and people working in animal husbandry (31.7%). All patients had histories of contact with diseased animals and animal products. Penicillin-group antibiotics (78%) were most commonly used in treatment. One patient (1.2%) died from anthrax meningitis. The mean length of hospitalization was 8.30 ± 5.36 days. Anthrax is an endemic disease of economic and social significance for the region. Effective public health control measures, risk group education, vaccination of animals, and decontamination procedures will reduce the number of cases.

  16. Russian vaccines against especially dangerous bacterial pathogens

    Science.gov (United States)

    Feodorova, Valentina A; Sayapina, Lidiya V; Corbel, Michael J; Motin, Vladimir L

    2014-01-01

    In response to the epidemiological situation, live attenuated or killed vaccines against anthrax, brucellosis, cholera, glanders, plague and tularemia were developed and used for immunization of at-risk populations in the Former Soviet Union. Certain of these vaccines have been updated and currently they are used on a selective basis, mainly for high risk occupations, in the Russian Federation. Except for anthrax and cholera these vaccines currently are the only licensed products available for protection against the most dangerous bacterial pathogens. Development of improved formulations and new products is ongoing. PMID:26038506

  17. Anthrax Meningitis - Report Of An Autopsied Case

    Directory of Open Access Journals (Sweden)

    Mahadevan A

    1999-01-01

    Full Text Available Anthrax is a rare cause of hemorrhagic meningitis in man. This report illustrates the characteristic hemorrhagic manifestations in the brain of a patient dying of anthrax meningitis secondary to overwhelming bacteremia. Gross examination of the brain revealed a thick dense subarachnoid hemorrhage with numerous petechial hemorrhages in the cortex. Histologically, meningoencephalitis with vascular necrosis, edema, perivascular cortical hemorrhages and clumps of Gram positive bacilli in the vascular lumen and invading vessel wall were the salient features. The anthrax bacillus was isolated from CSF and brain tissue and further its pathogenecity was confirmed by animal inoculation.

  18. Inhalation anthrax in a home craftsman.

    Science.gov (United States)

    Suffin, S C; Carnes, W H; Kaufmann, A F

    1978-09-01

    Inhalation anthrax with complicating subarachnoid hemorrhage due to simultaneous infection with two capsular biotypes of Bacillus anthracis of different virulence for the mouse is reported. The patient, a home craftsman, acquired his infection from imported animal-origin yarn.

  19. List of Contractors to Support Anthrax Remediation

    Energy Technology Data Exchange (ETDEWEB)

    Judd, Kathleen S.; Lesperance, Ann M.

    2010-05-14

    This document responds to a need identified by private sector businesses for information on contractors that may be qualified to support building remediation efforts following a wide-area anthrax release.

  20. Atomic structure of anthrax protective antigen pore elucidates toxin translocation.

    Science.gov (United States)

    Jiang, Jiansen; Pentelute, Bradley L; Collier, R John; Zhou, Z Hong

    2015-05-28

    Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. Protective antigen is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. On the basis of biochemical and electrophysiological results, researchers have proposed that a phi (Φ)-clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses protein translocation via a charge-state-dependent Brownian ratchet. Although atomic structures of protective antigen prepores are available, how protective antigen senses low pH, converts to active pore, and translocates lethal factor and oedema factor are not well defined without an atomic model of its pore. Here, by cryo-electron microscopy with direct electron counting, we determine the protective antigen pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic Φ-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low pH is sensed and the membrane-spanning channel is formed.

  1. Advances in Anthrax Detection: Overview of Bioprobes and Biosensors.

    Science.gov (United States)

    Kim, Joungmok; Gedi, Vinayakumar; Lee, Sang-Choon; Cho, Jun-Haeng; Moon, Ji-Young; Yoon, Moon-Young

    2015-06-01

    Anthrax is an infectious disease caused by Bacillus anthracis. Although anthrax commonly affects domestic and wild animals, it causes a rare but lethal infection in humans. A variety of techniques have been introduced and evaluated to detect anthrax using cultures, polymerase chain reaction, and immunoassays to address the potential threat of anthrax being used as a bioweapon. The high-potential harm of anthrax in bioterrorism requires sensitive and specific detection systems that are rapid, field-ready, and real-time monitoring. Here, we provide a systematic overview of anthrax detection probes with their potential applications in various ultra-sensitive diagnostic systems.

  2. Anthrax immunization of free-ranging Roan Antelope Hippotragus Equinus in the Kruger National Park

    Directory of Open Access Journals (Sweden)

    V. de Vos

    1973-07-01

    Full Text Available An aerial method of immunization is presented as afeasible means of vaccinating free-ranging roan antelope Hippotragus equinus against anthrax in the Kruger National Park. Themethod is described in detail and the results, obtained aftertwo consecutive years of application, are noted, tabulated andevaluated. A helicopter and a fixed wing aircraft were success-fully utilized in the location of widely dispersed roan antelopeherds and to bring the operator within effective firing rangeof the animal to be darted. A disposable projectile syringe,which simultaneously administers vaccine and effectively marksthe animal for later identification, is considered a vital part inthe successful implementation of the aerial method of immunization.

  3. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge.

    Science.gov (United States)

    Devera, T Scott; Prusator, Dawn K; Joshi, Sunil K; Ballard, Jimmy D; Lang, Mark L

    2015-06-25

    Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC) to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI), and hepatic alanine aminotransferase (ALT), and aspartate aminotransferase (AST), it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.

  4. Intramuscular delivery of adenovirus serotype 5 vector expressing humanized protective antigen induces rapid protection against anthrax that may bypass intranasally originated preexisting adenovirus immunity.

    Science.gov (United States)

    Wu, Shipo; Zhang, Zhe; Yu, Rui; Zhang, Jun; Liu, Ying; Song, Xiaohong; Yi, Shaoqiong; Liu, Ju; Chen, Jianqin; Yin, Ying; Xu, Junjie; Hou, Lihua; Chen, Wei

    2014-02-01

    Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 10⁸ infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD₅₀) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.

  5. Anthrax

    Science.gov (United States)

    1984-11-21

    rate, and congested hmorrhagic mucosae (1). Other symptoms -7- may Include ruminal stasis, anorexia, abortion in pregnant cows, discolored or blood...calcareous soils, subject to periodic flooding and formation of small pools which contain decaying plant matter, provide suitable conditions for growth of the

  6. Anthrax

    Science.gov (United States)

    ... Y.: The McGraw-Hill Companies; 2012. http://www.accessmedicine.com/resourceTOC.aspx?resourceID=4. Accessed Feb. 25, ... N.Y.: The McGraw-Hill Companies; 2006. http://accessmedicine.mhmedical.com/content.aspx?bookid=366&Sectionid=39825485. ...

  7. Anthrax toxin-induced rupture of artificial lipid bilayer membranes

    Science.gov (United States)

    Nablo, Brian J.; Panchal, Rekha G.; Bavari, Sina; Nguyen, Tam L.; Gussio, Rick; Ribot, Wil; Friedlander, Art; Chabot, Donald; Reiner, Joseph E.; Robertson, Joseph W. F.; Balijepalli, Arvind; Halverson, Kelly M.; Kasianowicz, John J.

    2013-08-01

    We demonstrate experimentally that anthrax toxin complexes rupture artificial lipid bilayer membranes when isolated from the blood of infected animals. When the solution pH is temporally acidified to mimic that process in endosomes, recombinant anthrax toxin forms an irreversibly bound complex, which also destabilizes membranes. The results suggest an alternative mechanism for the translocation of anthrax toxin into the cytoplasm.

  8. A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys.

    Science.gov (United States)

    Kachura, Melissa A; Hickle, Colin; Kell, Sariah A; Sathe, Atul; Calacsan, Carlo; Kiwan, Radwan; Hall, Brian; Milley, Robert; Ott, Gary; Coffman, Robert L; Kanzler, Holger; Campbell, John D

    2016-01-01

    Nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of APCs, have shown substantial promise for enhanced immunopotentiation. We investigated the adjuvant activity of synthetic oligonucleotides containing CpG-rich motifs linked to the sucrose polymer Ficoll, forming soluble 50-nm particles (DV230-Ficoll), each containing >100 molecules of the TLR9 ligand, DV230. DV230-Ficoll was evaluated as an adjuvant for a candidate vaccine for anthrax using recombinant protective Ag (rPA) from Bacillus anthracis. A single immunization with rPA plus DV230-Ficoll induced 10-fold higher titers of toxin-neutralizing Abs in cynomolgus monkeys at 2 wk compared with animals immunized with equivalent amounts of monomeric DV230. Monkeys immunized either once or twice with rPA plus DV230-Ficoll were completely protected from challenge with 200 LD50 aerosolized anthrax spores. In mice, DV230-Ficoll was more potent than DV230 for the induction of innate immune responses at the injection site and draining lymph nodes. DV230-Ficoll was preferentially colocalized with rPA in key APC populations and induced greater maturation marker expression (CD69 and CD86) on these cells and stronger germinal center B and T cell responses, relative to DV230. DV230-Ficoll was also preferentially retained at the injection site and draining lymph nodes and produced fewer systemic inflammatory responses. These findings support the development of DV230-Ficoll as an adjuvant platform, particularly for vaccines such as for anthrax, for which rapid induction of protective immunity and memory with a single injection is very important.

  9. Protocol for Real-Time PCR Identification of Anthrax Spores from Nasal Swabs after Broth Enrichment

    Science.gov (United States)

    Oggioni, Marco R.; Meacci, Francesca; Carattoli, Alessandra; Ciervo, Alessandra; Orru, Germano; Cassone, Antonio; Pozzi, Gianni

    2002-01-01

    A mass-screening protocol for the diagnosis of anthrax from nasal swabs based on an enrichment step in liquid medium was devised. Incubation for growth was performed in autoclavable vials and racks which allow real-time PCR analysis of sterilized cultures. A dual-color PCR was set up with primers and probes for the chromosomal marker rpoB and the plasmid marker lef. Specific primer and probe sets were designed for the differentiation of Bacillus anthracis from B. cereus and for the differentiation of the Sterne vaccine strain from field isolates and the Ames strain, which was used in the recent anthrax bioterrorist attack. The present protocol thus combines the high specificity and sensitivity of real-time PCR with excellent biosafety and the low hands-on time necessary for the processing of large numbers of samples, which is extremely important during control programs involving the processing of large numbers of samples. PMID:12409358

  10. Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women.

    Science.gov (United States)

    Meaney-Delman, Dana; Zotti, Marianne E; Creanga, Andreea A; Misegades, Lara K; Wako, Etobssie; Treadwell, Tracee A; Messonnier, Nancy E; Jamieson, Denise J

    2014-02-01

    In August 2012, the Centers for Disease Control and Prevention, in partnership with the Association of Maternal and Child Health Programs, convened a meeting of national subject matter experts to review key clinical elements of anthrax prevention and treatment for pregnant, postpartum, and lactating (P/PP/L) women. National experts in infectious disease, obstetrics, maternal fetal medicine, neonatology, pediatrics, and pharmacy attended the meeting, as did representatives from professional organizations and national, federal, state, and local agencies. The meeting addressed general principles of prevention and treatment for P/PP/L women, vaccines, antimicrobial prophylaxis and treatment, clinical considerations and critical care issues, antitoxin, delivery concerns, infection control measures, and communication. The purpose of this meeting summary is to provide updated clinical information to health care providers and public health professionals caring for P/PP/L women in the setting of a bioterrorist event involving anthrax.

  11. Serological anthrax surveillance in wild boar (Sus scrofa) in Ukraine.

    Science.gov (United States)

    Bagamian, Karoun H; Skrypnyk, Artem; Rodina, Yana; Bezymennyi, Maksym; Nevolko, Oleg; Skrypnyk, Valeriy; Blackburn, Jason K

    2014-08-01

    Anthrax, caused by Bacillus anthracis, is an acute disease affecting wildlife, livestock, and humans worldwide, although its impact on these populations is underappreciated. In Ukraine, surveillance is passive, and anthrax is often detected in livestock. However, wildlife is not subject to surveillance, although anthrax deaths (such as in wild boar, Sus scrofa) have been documented. The wild boar is a plentiful and widespread species in Ukraine and is frequently hunted. We initiated a screening study testing Ukrainian wild boar blood samples for antibodies to B. anthracis. We mapped results relative to known livestock anthrax hotspots. We discovered evidence of exposure in wild boar up to 35 km from livestock anthrax hotspots and over 400 km from previous anthrax reports in boars. We make recommendations about using wildlife species as biosentinels for anthrax in Ukraine.

  12. 75 FR 59729 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-09-28

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological... for protective antigen-based anthrax vaccines for a post-exposure prophylaxis indication using...

  13. Biological Weapons and Bioterorism Threats: The Role of Vaccines in Protecting the Military and Civilian Sectors

    Science.gov (United States)

    2013-05-16

    lowest risk, most effective protection – More effective with fewer adverse effects than antibiotics or other treatments – Enable force projection by...Plague • Anthrax Vaccine Adsorbed • Botulinum Toxoids* • Tularemia Vaccine* • Smallpox vaccine (Vaccinia Virus, Cell Culture-derived)* • Equine

  14. [Female patient with cutaneous anthrax in Belgium

    NARCIS (Netherlands)

    Gyssens, I.C.J.; Weyns, D.; Kullberg, B.J.; Ursi, J.P.

    2001-01-01

    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 ba

  15. Periorbital cellulitis due to cutaneous anthrax.

    Science.gov (United States)

    Gilliland, Grant; Starks, Victoria; Vrcek, Ivan; Gilliland, Connor

    2015-12-01

    Virgil's plague of the ancient world, Bacillus anthracis, is rare in developed nations. Unfortunately rural communities across the globe continue to be exposed to this potentially lethal bacterium. Herein we report a case of periorbital cutaneous anthrax infection in a 3-year-old girl from the rural area surrounding Harare, Zimbabwe with a brief review of the literature.

  16. An old friend: Anthrax in the Netherlands

    NARCIS (Netherlands)

    Koene, M.G.J.; Rosa, De M.; Spierenburg, M.A.H.; Jacobi, A.; Roest, H.I.J.

    2015-01-01

    In November 2013, bones covered with quicklime were discovered at a construction site near Nijmegen. According to regulations samples were sent to the national reference laboratory (Central Veterinary Institute, CVI), based on the suspicion of anthrax. Laboratory testing confirmed the presence of Ba

  17. Molecular determinants for a cardiovascular collapse in anthrax.

    Science.gov (United States)

    Brojatsch, Jurgen; Casadevall, Arturo; Goldman, David L

    2014-01-01

    Bacillus anthracis releases two bipartite proteins, lethal toxin and edema factor, that contribute significantly to the progression of anthrax-associated shock. As blocking the anthrax toxins prevents disease, the toxins are considered the main virulence factors of the bacterium. The anthrax bacterium and the anthrax toxins trigger multi-organ failure associated with enhanced vascular permeability, hemorrhage and cardiac dysfunction in animal challenge models. A recent study using mice that either lacked the anthrax toxin receptor in specific cells and corresponding mice expressing the receptor in specific cell types demonstrated that cardiovascular cells are critical for disease mediated by anthrax lethal toxin. These studies are consistent with involvement of the cardiovascular system, and with an increase of cardiac failure markers observed in human anthrax and in animal models using B. anthracis and anthrax toxins. This review discusses the current state of knowledge regarding the pathophysiology of anthrax and tries to provide a mechanistic model and molecular determinants for the circulatory shock in anthrax.

  18. The evaluation of clinical and laboratory findings of 63 inpatient with cutaneous anthrax: Characteristics of cutaneous anthrax in Turkey

    Directory of Open Access Journals (Sweden)

    Hatice Uce Özkol

    2014-12-01

    Full Text Available Background and Design: Despite a very uncommon disease in developed countries, cutaneous anthrax (CA is currently endemic in our countries. In this study, we aimed to bring out characteristic of anthrax of Turkey by comparing our results and the other CA reports in Turkey. Materials and Methods: Sixty three inpatients with CA between October 2009 and December 2012 were investigated retrospectively. All patients were diagnosed CA by clinical finding and/or microbiological examination. The demographic characteristics patient, routine tests, wound culture and gram staining results were recorded. Results were recorded on statistical program of SPSS 13.0 and were written using percent (%. Results: There were 63 inpatients (41 female (65.1%, 22 male (34.9%, mean age 35.9 years range10-83. Forty nine patients (77.8% had a history of contact with animals or animal product. Thirty-eight (60.3% and twenty-one (33.3% patients were found in the summer and fall season, respectively. Gram staining and culture were performed in 51 patients. Gram-positive bacilli were detected in 17 patients (33.3% by gram smear. Bacillus anthracis bacilli were produced in 11 patients (21.5% in cultures test. The lesions were mostly seen on the left hand (30.2%. Penicillin was most frequently preferred in treatment of CA (87.3%. Conclusion: CA is still endemic in Eastern Anatolia and continues to increase in recent years. Women living in the villages in which income is obtained from buying and selling of animals constitute the most important risk group. Preventive actions such as training of the risky society, vaccination of animals, and obstructing of illegal animal entries across the border, will reduce the incidence of CA.

  19. Meningoencephalitis due to anthrax: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Yildirim, Hanefi; Koc, Mustafa; Murat, Ayse [Firat University, Department of Radiology, Elazig (Turkey); Kabakus, Nimet; Incekoey Girgin, Feyza [Firat University, Department of Paediatric Neurology, Elazig (Turkey)

    2006-11-15

    Anthrax is primarily a disease of herbivores, but it also causes cutaneous, respiratory and gastrointestinal infections in humans. Bacillus anthracis is an uncommon cause of meningitis and generally produces a haemorrhagic meningoencephalitis. We present the CT and MR findings of anthrax meningoencephalitis due to the cutaneous form of anthrax in a 12-year-old boy. They showed focal intracerebral haemorrhage with leptomeningeal enhancement. (orig.)

  20. Human anthrax as a re-emerging disease.

    Science.gov (United States)

    Doganay, Mehmet; Demiraslan, Hayati

    2015-01-01

    Anthrax is primarily a disease of herbivores and the etiological agent is B. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. Bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. For these reasons, B. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the infectious agent. The disease most commonly affects wild and domestic mammals. Human are secondarily infected by contact with infected animals and contaminated animal products or directly expose to B. anthracis spores. Anthrax occurs worldwide. This infection is still endemic or hyperendemic in both animals and humans in some part of areas of the world; particularly in Middle East, West Africa, Central Asia, some part of India, South America. However, some countries are claiming free of anthrax, and anthrax has become a re-emerging disease in western countries with the intentional outbreak. Currently, anthrax is classified according to its setting as (1) naturally occurring anthrax, (2) bioterrorism-related anthrax. Vast majority of human anthrax are occurring as naturally occurring anthrax in the world. It is also a threaten disease for western countries. The aim of this paper is to review the relevant patents, short historical perspective, microbiological and epidemiological features, clinical presentations and treatment.

  1. New insights into gastrointestinal anthrax infection.

    Science.gov (United States)

    Owen, Jennifer L; Yang, Tao; Mohamadzadeh, Mansour

    2015-03-01

    Bacterial infections are the primary cause of gastrointestinal (GI) disorders in both developing and developed countries, and are particularly dangerous for infants and children. Bacillus anthracis is the 'archetype zoonotic' pathogen; no other infectious disease affects such a broad range of species, including humans. Importantly, there are more case reports of GI anthrax infection in children than inhalational disease. Early diagnosis is difficult and widespread systemic disease develops rapidly. This review highlights new findings concerning the roles of the gut epithelia, commensal microbiota, and innate lymphoid cells (ILCs) in initiation of disease and systemic dissemination in animal models of GI anthrax, the understanding of which is crucial to designing alternative therapies that target the establishment of infection.

  2. Challenges in Disposing of Anthrax Waste

    Energy Technology Data Exchange (ETDEWEB)

    Lesperance, Ann M.; Stein, Steven L.; Upton, Jaki F.; Toomey, Christopher

    2011-09-01

    Disasters often create large amounts of waste that must be managed as part of both immediate response and long-term recovery. While many federal, state, and local agencies have debris management plans, these plans often do not address chemical, biological, and radiological contamination. The Interagency Biological Restoration Demonstration’s (IBRD) purpose was to holistically assess all aspects of an anthrax incident and assist the development of a plan for long-term recovery. In the case of wide-area anthrax contamination and the follow-on response and recovery activities, a significant amount of material will require decontamination and disposal. Accordingly, IBRD facilitated the development of debris management plans to address contaminated waste through a series of interviews and workshops with local, state, and federal representatives. The outcome of these discussion was the identification of three primary topical areas that must be addressed: 1) Planning; 2) Unresolved research questions, and resolving regulatory issues.

  3. Anthrax phylogenetic structure in Northern Italy

    Directory of Open Access Journals (Sweden)

    Corrò Michela

    2011-07-01

    Full Text Available Abstract Background Anthrax has almost disappeared from mainland Europe, except for the Mediterranean region where cases are still reported. In Central and South Italy, anthrax is enzootic, but in the North there are currently no high risk areas, with only sporadic cases having been registered in the last few decades. Regional genetic and molecular characterizations of anthrax in these regions are still lacking. To investigate the potential molecular diversity of Bacillus anthracis in Northern Italy, canonical Single nucleotide polymorphism (canSNP and Multilocus variable number tandem repeat analysis (MLVA genotyping was performed against all isolates from animal outbreaks registered in the last twenty years in the region. Findings Six B. anthracis strains were analyzed. The canSNP analysis indicates the presence of three sublineages/subgroups each of which belong to one of the 12 worldwide CanSNP genotypes: B.Br.CNEVA (3 isolates, A.Br.005/006 (1 isolates and A.008/009 (2 isolate. The latter is the dominant canSNP genotype in Italy. The 15-loci MLVA analysis revealed five different genotypes among the isolates. Conclusions The major B branch and the A.Br.005/006 were recovered in the Northeast region. The genetic structure of anthrax discovered in this area differs from the rest of the country, suggesting the presence of a separate and independent B. anthracis molecular evolution niche. Although the isolates analyzed in this study are limited in quantity and representation, these results indicate that B. anthracis genetic diversity changes around the Alps.

  4. An Outbreak Of Human Anthrax : A Report Of 15 Cases Of Cutaneous Anthrax

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    2000-01-01

    Full Text Available Anthrax, a zoonotic illness of herbivorous animals has caused epidemics in livestock and in man since antiquity. In India, the disease continues to be endemic, resulting in a few sporadic cases and outbreaks in human population. Such an outbreak was noted at our institute. Clinical and laboratory data of 15 cases of cutaneous anthrax recorded between July 1998 to June 2000 at the Department of Dermatology and STD. JIPMER hospital, Pondicherry was reviewed. There were 8 males and 7 females in our series of 15, with a mean age of 20.3 years (range 11 months to 56 years. The children (10 outnumbered the adults (5. In most of the cases (9 there was history of death of cattle, sheep or goat in the house or in the neighbourhood. The commonest site of cutaneous anthrax was face (7 cases. Regional lymphadenitis occurred in one case and systemic features like fever in four cases. Majority of our cases responded favourably to crystalline penicillin. Smear taken from the vesicle fluid and eschar demonstrated typical large and thick Gram positive bacilli singly or in short chains. The organism could be cultured from cutaneous lesion in six cases only and blood culture was positive for Bacillus anthracis in one case. Cutaneous anthrax is the commonest form of human anthrax. There is increasing evidence to suggest that files and mosquitoes play a role in the transmission of Bacillus anthracis to human beings. Since 20% of untreated cases of cutaneous anthrax develop bacteraemia which leads to rapid death, it is important that the disease is recognized and treated earnestly.

  5. Dendritic Cells Endocytose Bacillus Anthracis Spores: Implications for Anthrax Pathogenesis

    Science.gov (United States)

    2007-11-02

    Dendritic Cells Endocytose Bacillus anthracis Spores: Implications for Anthrax Pathogenesis1 Katherine C. Brittingham,* Gordon Ruthel,* Rekha G...germination and dissemination of spores. Found in high frequency throughout the respiratory track, dendritic cells (DCs) routinely take up foreign...COVERED - 4. TITLE AND SUBTITLE Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesis, The Journal of

  6. Two anthrax cases with soft tissue infection, severe oedema and sepsis in Danish heroin users

    DEFF Research Database (Denmark)

    Russell, Lene; Pedersen, Michael; Jensen, Andreas V

    2013-01-01

    Anthrax had become extremely rare in Europe, but in 2010 an outbreak of anthrax among heroin users in Scotland increased awareness of contaminated heroin as a source of anthrax. We present the first two Danish cases of injectional anthrax and discuss the clinical presentations, which included both...

  7. Revisiting the Concept of Targeting Only Bacillus anthracis Toxins as a Treatment for Anthrax.

    Science.gov (United States)

    Glinert, Itai; Bar-David, Elad; Sittner, Assa; Weiss, Shay; Schlomovitz, Josef; Ben-Shmuel, Amir; Mechaly, Adva; Altboum, Zeev; Kobiler, David; Levy, Haim

    2016-08-01

    Protective antigen (PA)-based vaccines are effective in preventing the development of fatal anthrax disease both in humans and in relevant animal models. The Bacillus anthracis toxins lethal toxin (lethal factor [LF] plus PA) and edema toxin (edema factor [EF] plus PA) are essential for the establishment of the infection, as inactivation of these toxins results in attenuation of the pathogen. Since the toxins reach high toxemia levels at the bacteremic stages of the disease, the CDC's recommendations include combining antibiotic treatment with antitoxin (anti-PA) immunotherapy. We demonstrate here that while treatment with a highly potent neutralizing monoclonal antibody was highly efficient as postexposure prophylaxis treatment, it failed to protect rabbits with any detectable bacteremia (≥10 CFU/ml). In addition, we show that while PA vaccination was effective against a subcutaneous spore challenge, it failed to protect rabbits against systemic challenges (intravenous injection of vegetative bacteria) with the wild-type Vollum strain or a toxin-deficient mutant. To test the possibility that additional proteins, which are secreted by the bacteria under pathogenicity-stimulating conditions in vitro, may contribute to the vaccine's potency, we immunized rabbits with a secreted protein fraction from a toxin-null mutant. The antiserum raised against the secreted fraction reacts with the bacteria in an immunofluorescence assay. Immunization with the secreted protein fraction did not protect the rabbits against a systemic challenge with the fully pathogenic bacteria. Full protection was obtained only by a combined vaccination with PA and the secreted protein fraction. Therefore, these results indicate that an effective antiserum treatment in advanced stages of anthrax must include toxin-neutralizing antibodies in combination with antibodies against bacterial cell targets.

  8. The Effect of Anthrax Bioterrorism on Emergency Department Presentation

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    Rodriguez, Robert M

    2005-01-01

    Full Text Available Study Objective: From September through December 2001, 22 Americans were diagnosed with anthrax, prompting widespread national media attention and public concern over bioterrorism. The purpose of this study was to determine the effect of the threat of anthrax bioterrorism on patient presentation to a West Coast emergency department (ED. Methods: This survey was conducted at an urban county ED in Oakland, CA between December 15, 2001 and February 15, 2002. During random 8-hour blocks, all adult patients presenting for flu or upper respiratory infection (URI symptoms were surveyed using a structured survey instrument that included standard visual numerical and Likert scales. Results: Eighty-nine patients were interviewed. Eleven patients (12% reported potential exposure risk factors. Eighty percent of patients watched television, read the newspaper, or listened to the radio daily, and 83% of patients had heard about anthrax bioterrorism. Fifty-five percent received a chest x-ray, 10% received either throat or blood cultures, and 28% received antibiotics. Twenty-one percent of patients surveyed were admitted to the hospital. Most patients were minimally concerned that they may have contracted anthrax (mean=3.3±3.3 where 0=no concern and 10=extremely concerned. Patient concern about anthrax had little influence on their decision to visit the ED (mean=2.8±3.0 where 0=no influence and 10=greatly influenced. Had they experienced their same flu or URI symptoms one year prior to the anthrax outbreak, 91% of patients stated they would have sought medical attention. Conclusions: After considerable exposure to media reports about anthrax, most patients in this urban West Coast ED population were not concerned about anthrax infection. Fear of anthrax had little effect on decisions to come to the ED, and most would have sought medical help prior to the anthrax outbreak.

  9. Anthrax Vaccine Powder Formulations for Nasal Mucosal Delivery

    Science.gov (United States)

    2005-08-04

    95 Sodium citrate 0.1 M 94 Trehalose 20.00% 94 Malic acid 0.15 M 83 Trehalose 10.00% 78 Brij 35 0.05% 72 Tween 80 0.10% 46 Brij 35 0.01% 41 Tween 80 0.05...23 Tween 20 0.05% 22 Tween 80 0.01% 17 Tween 20 0.01% 16 Tween 20 0.10% 14 Dextran T40 0.1 12 Dextran T40 2.5 1 Brij 35 0.10% 0 Dextran T40 1.0

  10. Risk Assessment of Anthrax Threat Letters

    Science.gov (United States)

    2001-09-01

    risk. Résumé Depuis quelques années, il arrive de plus en plus souvent que des lettres censées contenir l’agent de la maladie du charbon (ou...Depuis quelques années, il arrive de plus en plus souvent que des lettres censées contenir l’agent de la maladie du charbon (ou anthrax) soient...Contracting Agency : Tasking Agency: 9. ORIGINATORS DOCUMENT NO. Technical Report DRES-TR- 2001-048 10. CONTRACT GRANT AND/OR PROJECT NO. 11

  11. Injectional anthrax - new presentation of an old disease.

    Science.gov (United States)

    Berger, T; Kassirer, M; Aran, A A

    2014-08-14

    Bacillus anthracis infection (anthrax) has three distinct clinical presentations depending on the route of exposure: cutaneous, gastrointestinal and inhalational anthrax. Each of these can lead to secondary bacteraemia and anthrax meningitis. Since 2009,anthrax has emerged among heroin users in Europe,presenting a novel clinical manifestation, 'injectional anthrax', which has been attributed to contaminated heroin distributed throughout Europe; before 2009 only one case was reported. During 2012 and 2013,new cases of injectional anthrax were diagnosed in Denmark, France, Germany, and the United Kingdom.Here we present a comprehensive review of the literature and information derived from different reporting systems until 31 December 2013. Overall 70 confirmed cases were reported, with 26 fatalities (37% case fatality rate).The latest two confirmed cases occurred in March 2013. Thirteen case reports have been published,describing 18 confirmed cases. Sixteen of these presented as a severe soft tissue infection that differed clinically from cutaneous anthrax, lacked the characteristic epidemiological history of animal contact and ten cases required complimentary surgical debridement. These unfamiliar characteristics have led to delays of three to 12 days in diagnosis, inadequate treatment and a high fatality rate. Clinicians' awareness of this recently described clinical entity is key for early 'and successful management of patients.

  12. A Case of Fatal Gastrointestinal Anthrax in North Eastern Iran

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    Seyed Ahmad Hashemi

    2015-01-01

    Full Text Available Background. Bacillus species are aerobic or facultative anaerobic, gram-positive, or gram-variable spore-forming rods. They are ubiquitous in the environmental sources. Bacillus anthracis may usually cause three forms of anthrax: inhalation, gastrointestinal, and cutaneous. The gastrointestinal (GI anthrax develops after eating contaminated meat. In this paper we report septic intestinal anthrax. Case Presentation. We report an isolation of Bacillus anthracis from blood culture of patient with intestinal anthrax. Bacillus anthracis was isolated from a blood culture of a 34-year-old man who had a history of severe abdominal pain, bloody diarrhea, nausea, vomiting, fever, sweating, and lethargy within 4 to 5 days after eating the meat of domestic goat. He had evidence of severe infection and septic shock and did not respond to treatments and subsequently expired 9 hours after hospitalization. Conclusion. Gastrointestinal anthrax is characterized by rapid onset, fever, and septicemia. Rapid diagnosis and prompt initiation of antibiotic therapy can help in survival. Most of previous cases of septicemic anthrax were related to injection drug users but, in our case, septicemia occurred after gastrointestinal anthrax.

  13. Screen-printed fluorescent sensors for rapid and sensitive anthrax biomarker detection

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Inkyu; Oh, Wan-Kyu; Jang, Jyongsik, E-mail: jsjang@plaza.snu.ac.kr

    2013-05-15

    Highlights: •We fabricated flexible anthrax sensors with a simple screen-printing method. •The sensors selectively detected B. anthracis biomarker. •The sensors provide the visible alarm against anthrax attack. -- Abstract: Since the 2001 anthrax attacks, efforts have focused on the development of an anthrax detector with rapid response and high selectivity and sensitivity. Here, we demonstrate a fluorescence sensor for detecting anthrax biomarker with high sensitivity and selectivity using a screen-printing method. A lanthanide–ethylenediamine tetraacetic acid complex was printed on a flexible polyethersulfone film. Screen-printing deposition of fluorescent detecting moieties produced fluorescent patterns that acted as a visual alarm against anthrax.

  14. Antitoxin Treatment of Inhalation Anthrax: A Systematic Review.

    Science.gov (United States)

    Huang, Eileen; Pillai, Satish K; Bower, William A; Hendricks, Katherine A; Guarnizo, Julie T; Hoyle, Jamechia D; Gorman, Susan E; Boyer, Anne E; Quinn, Conrad P; Meaney-Delman, Dana

    2015-01-01

    Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax

  15. A retrospective study on the epidemiology of anthrax, foot and mouth disease, haemorrhagic septicaemia, peste des petits ruminants and rabies in Bangladesh, 2010-2012.

    Directory of Open Access Journals (Sweden)

    Shankar P Mondal

    Full Text Available Anthrax, foot and mouth disease (FMD, haemorrhagic septicaemia (HS, peste des petits ruminants (PPR and rabies are considered to be endemic in Bangladesh. This retrospective study was conducted to understand the geographic and seasonal distribution of these major infectious diseases in livestock based on data collected through passive surveillance from 1 January 2010 to 31 December 2012. Data analysis for this period revealed 5,937 cases of anthrax, 300,333 of FMD, 13,436 of HS, 247,783 of PPR and 14,085 cases of dog bite/rabies. While diseases were reported in almost every district of the country, the highest frequency of occurrence corresponded to the susceptible livestock population in the respective districts. There was no significant difference in the disease occurrences between districts bordering India/Myanmar and non-border districts (p>0.05. Significantly higher (p<0.01 numbers of anthrax (84.5%, FMD (88.3%, HS (84.9% and dog bite/rabies (64.3% cases were reported in cattle than any other species. PPR cases were reported mostly (94.8% in goats with only isolated cases (5.2% in sheep. The diseases occur throughout the year with peak numbers reported during June through September and lowest during December through April, with significant differences (p<0.01 between the months. The annual usages of vaccines for anthrax, FMD, HS and PPR were only 7.31%, 0.61%, 0.84% and 11.59% of the susceptible livestock population, respectively. Prophylactic vaccination against rabies was 21.16% of cases. There were significant differences (p<0.01 in the administration of anthrax, FMD and HS vaccines between border and non-border districts, but not PPR or rabies vaccines. We recommend that surveillance and reporting of these diseases need to be improved throughout the country. Furthermore, all suspected clinical cases should be confirmed by laboratory examination. The findings of this study can be used in the formulation of more effective disease

  16. Development of an acid-resistant Salmonella Typhi Ty21a attenuated vector for improved oral vaccine delivery

    Science.gov (United States)

    The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, T...

  17. [The time course of changes in cell immunological parameters during administration of live dry plague vaccine].

    Science.gov (United States)

    Bogacheva, N V; Darmov, I V; Borisevich, I V; Kriuchkov, A V; Pechenkin, D V

    2009-08-01

    The study of the time course of changes in cell immunological parameters by a magnetic separation technique in human beings during the administration of plague vaccine in relation to the immunological load revealed the higher blood levels of all T lymphocyte subpopulations on day 14 after vaccination. These changes are most typical of a primary vaccinated cohort. The increased frequency of plague vaccine administration and multiple immunizations with live plague, anthrax, and tularemia vaccines produce the time-course of changes in T lymphocyte populations (subpopulations) in response to the regular administration of plague vaccine. A high immunological load in man also promotes a significant reduction in the level of B lymphocytes.

  18. Development & validation of a quantitative anti-protective antigen IgG enzyme linked immunosorbent assay for serodiagnosis of cutaneous anthrax

    Directory of Open Access Journals (Sweden)

    N Ghosh

    2015-01-01

    Full Text Available Background & objectives: Anthrax caused by Bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. ELISA is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. The aims of this study were to develop and evaluate a quantitative ELISA for determination of IgG antibodies against B. anthracis protective antigen (PA in human cutaneous anthrax cases. Methods: Quantitative ELISA was developed using the recombinant PA for coating and standard reference serum AVR801 for quantification. A total of 116 human test and control serum samples were used in the study. The assay was evaluated for its precision, accuracy and linearity. Results: The minimum detection limit and lower limit of quantification of the assay for anti-PA IgG were 3.2 and 4 µg/ml, respectively. The serum samples collected from the anthrax infected patients were found to have anti-PA IgG concentrations of 5.2 to 166.3 µg/ml. The intra-assay precision per cent CV within an assay and within an operator ranged from 0.99 to 7.4 per cent and 1.7 to 3.9 per cent, respectively. The accuracy of the assay was high with a per cent error of 6.5 - 24.1 per cent. The described assay was found to be linear between the range of 4 to 80 ng/ml (R [2] =0.9982; slope=0.9186; intercept = 0.1108. Interpretation & conclusions: The results suggested that the developed assay could be a useful tool for quantification of anti-PA IgG response in human after anthrax infection or vaccination.

  19. Investigation and control of anthrax outbreak at the human-animal interface, Bhutan, 2010.

    Science.gov (United States)

    Thapa, Nirmal K; Tenzin; Wangdi, Karma; Dorji, Tshering; Migma; Dorjee, Jambay; Marston, Chung K; Hoffmaster, Alex R

    2014-09-01

    In 2010, we investigated anthrax outbreak in Bhutan. A total of 43 domestic animals died, and cutaneous anthrax developed in 9 persons, and 1 died. All affected persons had contact with the carcasses of infected animals. Comprehensive preparedness and response guidelines are needed to increase public awareness of anthrax in Bhutan.

  20. Anthrax Toxin-Expressing Bacillus cereus Isolated from an Anthrax-Like Eschar.

    Directory of Open Access Journals (Sweden)

    Chung K Marston

    Full Text Available Bacillus cereus isolates have been described harboring Bacillus anthracis toxin genes, most notably B. cereus G9241, and capable of causing severe and fatal pneumonias. This report describes the characterization of a B. cereus isolate, BcFL2013, associated with a naturally occurring cutaneous lesion resembling an anthrax eschar. Similar to G9241, BcFL2013 is positive for the B. anthracis pXO1 toxin genes, has a multi-locus sequence type of 78, and a pagA sequence type of 9. Whole genome sequencing confirms the similarity to G9241. In addition to the chromosome having an average nucleotide identity of 99.98% when compared to G9241, BcFL2013 harbors three plasmids with varying homology to the G9241 plasmids (pBCXO1, pBC210 and pBFH_1. This is also the first report to include serologic testing of patient specimens associated with this type of B. cereus infection which resulted in the detection of anthrax lethal factor toxemia, a quantifiable serum antibody response to protective antigen (PA, and lethal toxin neutralization activity.

  1. Anthrax Toxin-Expressing Bacillus cereus Isolated from an Anthrax-Like Eschar.

    Science.gov (United States)

    Marston, Chung K; Ibrahim, Hisham; Lee, Philip; Churchwell, George; Gumke, Megan; Stanek, Danielle; Gee, Jay E; Boyer, Anne E; Gallegos-Candela, Maribel; Barr, John R; Li, Han; Boulay, Darbi; Cronin, Li; Quinn, Conrad P; Hoffmaster, Alex R

    2016-01-01

    Bacillus cereus isolates have been described harboring Bacillus anthracis toxin genes, most notably B. cereus G9241, and capable of causing severe and fatal pneumonias. This report describes the characterization of a B. cereus isolate, BcFL2013, associated with a naturally occurring cutaneous lesion resembling an anthrax eschar. Similar to G9241, BcFL2013 is positive for the B. anthracis pXO1 toxin genes, has a multi-locus sequence type of 78, and a pagA sequence type of 9. Whole genome sequencing confirms the similarity to G9241. In addition to the chromosome having an average nucleotide identity of 99.98% when compared to G9241, BcFL2013 harbors three plasmids with varying homology to the G9241 plasmids (pBCXO1, pBC210 and pBFH_1). This is also the first report to include serologic testing of patient specimens associated with this type of B. cereus infection which resulted in the detection of anthrax lethal factor toxemia, a quantifiable serum antibody response to protective antigen (PA), and lethal toxin neutralization activity.

  2. Dances with anthrax: wolves (Canis lupus) kill anthrax bacteremic plains bison (Bison bison bison) in southwestern Montana.

    Science.gov (United States)

    Blackburn, Jason K; Asher, Valpa; Stokke, Stephen; Hunter, David L; Alexander, Kathleen A

    2014-04-01

    Bacillus anthracis, the cause of anthrax, was recovered from two plains bison (Bison bison bison) cows killed by wolves (Canis lupus) in Montana, USA, without associated wolf mortality in July 2010. This bison herd experienced an epizootic in summer 2008, killing ∼ 8% of the herd, the first documented in the region in several decades. No wolf deaths were associated with the 2008 event. Surveillance has continued since 2008, with research, ranch, and wildlife personnel diligent during summer. As part of this, we tested wolf-killed bison and elk (Cervus elaphus) for anthrax during the 2010 summer using lateral flow immunochromatographic assays (LFIA). Two bison cows were positive for protective antigen, confirming active bacteremia. The LFIA results were confirmed with traditional bacteriology recovering viable B. anthracis. No wolf fatalities were associated with the bison deaths, despite consuming the meat. Low-level anthrax occurrence in large, rough terrain landscapes remains difficult to detect, particularly if mortality in the herbivore host is not a consequence of infection. In these instances, surveillance of predators with large home ranges may provide a more sensitive indicator of anthrax emergence or reemergence in such systems. Though speculative, it is also possible that anthrax infection in the bison increased predation risk. These results also suggest B. anthracis remains a threat to wildlife and associated livestock in southwestern Montana.

  3. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  4. Bacillus anthracis Capsular Conjugates Elicit Chimpanzee Polyclonal Antibodies That Protect Mice from Pulmonary Anthrax.

    Science.gov (United States)

    Chen, Zhaochun; Schneerson, Rachel; Lovchik, Julie A; Dai, Zhongdong; Kubler-Kielb, Joanna; Agulto, Liane; Leppla, Stephen H; Purcell, Robert H

    2015-08-01

    The immunogenicity of Bacillus anthracis capsule (poly-γ-D-glutamic acid [PGA]) conjugated to recombinant B. anthracis protective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated. This study examines the polyclonal antibody response of the same animals. Preimmune antibodies to PGA with titers of >10(3) were detected in the chimpanzees. The maximal titer of anti-PGA was induced within 1 to 2 weeks following the 1st immunization, with no booster effects following the 2nd and 3rd immunizations. Thus, the anti-PGA response in the chimpanzees resembled a secondary immune response. Screening of sera from nine unimmunized chimpanzees and six humans revealed antibodies to PGA in all samples, with an average titer of 10(3). An anti-PA response was also observed following immunization with PGA-rPA conjugate, similar to that seen following immunization with rPA alone. However, in contrast to anti-PGA, preimmune anti-PA antibody titers and those following the 1st immunization were ≤300, with the antibodies peaking above 10(4) following the 2nd immunization. The polyclonal anti-PGA shared the MAb 11D epitope and, similar to the MAbs, exerted opsonophagocytic killing of B. anthracis. Most important, the PGA-TT-induced antibodies protected mice from a lethal challenge with virulent B. anthracis spores. Our data support the use of PGA conjugates, especially PGA-rPA targeting both toxin and capsule, as expanded-spectrum anthrax vaccines.

  5. Space Technology to Device that Destroys Pathogens Such As Anthrax

    Science.gov (United States)

    2002-01-01

    This is a photo of a technician at KES Science and Technology Inc., in Kernesaw, Georgia, assembling the AiroCide Ti02, an anthrax-killing device about the size of a small coffee table. The anthrax-killing air scrubber, AiroCide Ti02, is a tabletop-size metal box that bolts to office ceilings or walls. Its fans draw in airborne spores and airflow forces them through a maze of tubes. Inside, hydroxyl radicals (OH-) attack and kill pathogens. Most remaining spores are destroyed by high-energy ultraviolet photons. Building miniature greenhouses for experiments on the International Space Station has led to the invention of this device that annihilates anthrax, a bacteria that can be deadly when inhaled. The research enabling the invention started at the University of Wisconsin's (Madison) Center for Space Automation and Robotics (WCSAR), one of 17 NASA Commercial Space Centers. A special coating technology used in this anthrax-killing invention is also being used inside WCSAR-built plant growth units on the International Space Station. This commercial research is managed by the Space Product Development Program at the Marshall Space Flight Center.

  6. Anthrax toxin receptor 2-dependent lethal toxin killing in vivo.

    Directory of Open Access Journals (Sweden)

    Heather M Scobie

    2006-10-01

    Full Text Available Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2 have a related integrin-like inserted (I domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in the absence of metal ions, we reasoned that D683 mutant forms of PA might specifically interact with ANTXR2. We show here that this is the case. The differential ability of ANTXR1 and ANTXR2 to bind D683 mutant PA proteins was mapped to nonconserved receptor residues at the binding interface with PA domain 2. Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis.

  7. Cutaneous anthrax of the hand: Some clinical observations

    Directory of Open Access Journals (Sweden)

    Tuncali Dogan

    2004-01-01

    Full Text Available CONTEXT: Anthrax is a very rare disease in Europe and the United States. AIM: A case of cutaneous anthrax of the hand with a wide skin defect is presented and some clinical observations highlighted. CASE REPORT: A 56-year-old male patient with cutaneous anthrax attended our infectious diseases department with a swelling up to the upper arm. An urgent fasciotomy was undertaken with a diagnosis of compartment syndrome. A black eschar had formed on the dorsal surface of the hand. A superficial tangential escharectomy was performed. RESULTS: Viable fibrous tissue, about 4 to 5 mm in thickness over the extensor tendons, was found under the eschar. At the postoperative 2-year follow-up, remarkable healing was observed via skin grafting. CONCLUSIONS: Hand surgeons should be cautious against the compartment syndrome that may accompany cutaneous anthrax of the hand. A consistent viable fibrous tissue can be found below the eschar. The mechanism for the involvement of the hand dorsum needs further concern.

  8. AN OUTBREAK OF CUTANEOUS ANTHRAX IN TRIBAL AREAS OF VISAKHAPATNAM

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    G. Ajay Kumar

    2016-08-01

    Full Text Available BACKGROUND Anthrax is a disease of herbivorous animals. Humans incidentally acquire the cutaneous disease by handling infected dead animals and their products. Sporadic cases of human anthrax have been reported from Southern India. METHODS Fifteen tribal men, one woman, one child from various places near Paderu presented with painless ulcers associated with vesiculation and oedema of the surrounding skin on the extremities without any constitutional symptoms. There was a history of slaughtering and consumption of a dead goat ten days - 2 weeks prior to the development of skin lesions. Three days later another 19 members came from the same area with same complaints. Clinically, cutaneous anthrax was suspected and smears, swabs, and punch biopsies were taken for culture and identification by Polymerase Chain Reaction (PCR. All the cases were treated with intravenous antibiotics followed by oral antibiotics. Appropriate health authorities were alerted and proper control measures were employed. RESULTS Smears from the cutaneous lesions of some patients were found to be positive for Bacillus anthracis and this was confirmed by polymerase chain reaction. All the cases responded to antibiotics. CONCLUSION We report thirty six cases of cutaneous anthrax in a non-endemic district, Visakhapatnam, Andhra Pradesh.

  9. Growth medium for the rapid isolation and identification of anthrax

    Science.gov (United States)

    Kiel, Johnathan L.; Parker, Jill E.; Grubbs, Teri R.; Alls, John L.

    2000-07-01

    Anthrax has been recognized as a highly likely biological warfare or terrorist agent. The purpose of this work was to design a culture technique to rapidly isolate and identify `live' anthrax. In liquid or solid media form, 3AT medium (3-amino-L-tyrosine, the main ingredient) accelerated germination and growth of anthrax spores in 5 to 6 hours to a point expected at 18 to 24 hours with ordinary medium. During accelerated growth, standard definitive diagnostic tests such as sensitivity to lysis by penicillin or bacteriophage can be run. During this time, the bacteria synthesized a fluorescent and thermochemiluminescent polymer. Bacteria captured by specific antibody are, therefore, already labeled. Because living bacteria are required to generate the polymer, the test converts immunoassays for anthrax into viability assays. Furthermore, the polymer formation leads to the death of the vegetative form and non-viability of the spores produced in the medium. By altering the formulation of the medium, other microbes and even animal and human cells can be grown in it and labeled (including viruses grown in the animal or human cells).

  10. America’s Food: Does Anthrax Pose A Threat?

    Science.gov (United States)

    2002-04-01

    1.htm. 17 Jernigan. 18 Ibid. 19 Ibid. 20 Ibid. 21 Borio, Luciana ; et al. “Death Due to Bioterrorism-Related Inhalational Anthrax.” JAMA, Vol...13 December 2001. On-line. Internet, 4 March 2002. Available from http://www.ift.org/press/releases/terrorism/shtml. Borio, Luciana ; et al. “Death

  11. Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies

    Science.gov (United States)

    Ramirez, Karina; Ditamo, Yanina; Galen, James E.; Baillie, Les W. J.; Pasetti, Marcela F.

    2010-01-01

    The currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. Effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. We explored the use of the licensed live attenuated S. Typhi vaccine strain Ty21a expressing Bacillus anthracis protective antigen [Ty21a(PA)] followed PA-alum as a strategy for immunizing the pediatric population. Newborn mice primed with a single dose of Ty21a(PA) exhibited high frequencies of mucosal IgA-secreting B cells and IFN-γ-secreting T cells during the neonatal period, none of which was detected in newborns immunized with a single dose of PA-alum. Priming with Ty21a(PA) followed by PA-boost resulted in high levels of PA-specific IgG, toxin-neutralizing and opsonophagocytic antibodies and increased frequency of bone marrow IgG plasma cells and memory B cells compared with repeated immunization with PA-alum alone. Robust B and T cell responses developed even in the presence of maternal antibodies. The prime-boost protected against systemic and respiratory infection. Mucosal priming with a safe and effective S. Typhi-based anthrax vaccine followed by PA-boost could serve as a practical and effective prophylactic approach to prevent anthrax early in life. PMID:20619377

  12. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults.

    Science.gov (United States)

    Hendricks, Katherine A; Wright, Mary E; Shadomy, Sean V; Bradley, John S; Morrow, Meredith G; Pavia, Andy T; Rubinstein, Ethan; Holty, Jon-Erik C; Messonnier, Nancy E; Smith, Theresa L; Pesik, Nicki; Treadwell, Tracee A; Bower, William A

    2014-02-01

    The Centers for Disease Control and Prevention convened panels of anthrax experts to review and update guidelines for anthrax postexposure prophylaxis and treatment. The panels included civilian and military anthrax experts and clinicians with experience treating anthrax patients. Specialties represented included internal medicine, pediatrics, obstetrics, infectious disease, emergency medicine, critical care, pulmonology, hematology, and nephrology. Panelists discussed recent patients with systemic anthrax; reviews of published, unpublished, and proprietary data regarding antimicrobial drugs and anthrax antitoxins; and critical care measures of potential benefit to patients with anthrax. This article updates antimicrobial postexposure prophylaxis and antimicrobial and antitoxin treatment options and describes potentially beneficial critical care measures for persons with anthrax, including clinical procedures for infected nonpregnant adults. Changes from previous guidelines include an expanded discussion of critical care and clinical procedures and additional antimicrobial choices, including preferred antimicrobial drug treatment for possible anthrax meningitis.

  13. Genome Sequence of the Soviet/Russian Bacillus anthracis Vaccine Strain 55-VNIIVViM

    Science.gov (United States)

    Kotorashvili, Adam

    2016-01-01

    Bacillus anthracis strain 55-VNIIVViM is a live-attenuated nonencapsulated Soviet/Russian veterinary anthrax vaccine strain. We report here the genome of 55-VNIIVViM and confirm its phylogenetic placement in the global population structure of B. anthracis. PMID:28007853

  14. First Autochthonous Coinfected Anthrax in an Immunocompetent Patient

    Directory of Open Access Journals (Sweden)

    Parvaneh Afshar

    2015-01-01

    Full Text Available Cutaneous anthrax has a mortality rate of 20% if no antibacterial treatment is applied. The clinical manifestations of cutaneous anthrax are obviously striking, but coinfection may produce atypical lesions and mask the clinical manifestations and proper laboratory diagnosis. Anthrax is known to be more common in the Middle East and Iran is one of the countries in which the zoonotic form of anthrax may still be encountered. We report a case of a 19-years-old male who used to apply Venetian ceruse on his skin. Venetian ceruse (also known as Spirits of Saturn is an old cosmetic product used for skin whitening traditionally made from sheep’s spinal cord. The patient referred to the Referral Laboratory, Mazandaran University of Medical Sciences, Sari, Iran, with atypical dermatosis, pronounced pain, and oedema of the affected tissue. It was confirmed by both conventional and molecular analysis that culture was a mixture of Bacillus anthracis and Trichophyton interdigitale. The patient was initially treated with ceftriaxone (1000 mg/day for two weeks, gentamicin (1.5–2 mg/kg/day, terbinafine (200 mg/week for one month, and 1% clotrimazole cream (5 weeks two times per day which resulted in gradual improvement. No relapse could be detected after one-year follow-up. Anthrax infection might present a broader spectrum of symptoms than expected by clinicians. These unfamiliar characteristics may lead to delayed diagnosis, inadequate treatment, and higher mortality rate. Clinicians need to be aware of this issue in order to have successful management over this infection.

  15. Dismantling the Taboo against Vaccines in Pregnancy

    Directory of Open Access Journals (Sweden)

    Maurizio de Martino

    2016-06-01

    Full Text Available Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy.

  16. Dismantling the Taboo against Vaccines in Pregnancy

    Science.gov (United States)

    de Martino, Maurizio

    2016-01-01

    Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy. PMID:27338346

  17. Integrated MOSFET-Embedded-Cantilever-Based Biosensor Characteristic for Detection of Anthrax Simulant

    Energy Technology Data Exchange (ETDEWEB)

    Mostafa, Salwa [University of Tennessee, Knoxville (UTK); Lee, Ida [ORNL; Islam, Syed K [University of Tennessee, Knoxville (UTK); Eliza, Sazia A. [University of Tennessee, Knoxville (UTK); Shekhawat, Gajendra [Northwestern University, Evanston; Dravid, Vinayak [Northwestern University, Evanston; Tulip, Fahmida S [ORNL

    2011-01-01

    In this work, MOSFET-embedded cantilevers are configured as microbial sensors for detection of anthrax simulants, Bacillus thuringiensis. Anthrax simulants attached to the chemically treated gold-coated cantilever cause changes in the MOSFET drain current due to the bending of the cantilever which indicates the detection of anthrax simulant. Electrical properties of the anthrax simulant are also responsible for the change in the drain current. The test results suggest a detection range of 10 L of stimulant test solution (a suspension population of 1.3 107 colony-forming units/mL diluted in 40% ethanol and 60% deionized water) with a linear response of 31 A/ L.

  18. Clinical and epidemiological investigation of a fatal anthrax case in China.

    Science.gov (United States)

    Chen, Haiying; Bao, Wanguo; Wang, Yang; Zhang, Kaiyu; Wang, Feng

    2015-02-19

    Anthrax is a recessive infectious disease caused by the bacterium Bacillus anthracis, and is primarily a zoonotic disease. Until recently, Bacillus anthracis infections were relatively infrequent and confined to agrarian communities in underdeveloped countries. No anthrax cases were reported in Changchun City in the past few decades until a male patient from the Inner Mongolia Autonomous Region presented the anthrax disease manifestation. This paper describes an anthrax patient's diagnosis, isolation and treatment which involved institutions in two different Chinese provinces; the foci epidemiological investigation alongside with the outbreak management process, which is of great significance to control the spread of the recessive infection is also described.

  19. Development of a simple method for the rapid identification of organisms causing anthrax by coagglutination test.

    Science.gov (United States)

    Sumithra, T G; Chaturvedi, V K; Gupta, P K; Siju, S J; Susan, C; Bincy, J; Laxmi, U; Sunita, S C; Rai, A K

    2014-11-01

    A protective antigen (PA) based coagglutination test was optimized in the present study for the specific and sensitive identification of bacteria causing anthrax in a cost effective and less risky manner. The test showed 100% specificity and sensitivity up to 9 × 10(3) formalinized vegetative cells or 11 ng of PA. The optimized test also detected anthrax toxin directly from the serum as well as blood of anthrax infected animals indicating the potential application for direct diagnosis of anthrax under field conditions.

  20. Evaluation of the house fly Musca domestica as a mechanical vector for an anthrax.

    Directory of Open Access Journals (Sweden)

    Antonio Fasanella

    Full Text Available Anthrax is a disease of human beings and animals caused by the encapsulated, spore-forming, Bacillus anthracis. The potential role of insects in the spread of B. anthracis to humans and domestic animals during an anthrax outbreak has been confirmed by many studies. Among insect vectors, the house fly Musca domestica is considered a potential agent for disease transmission. In this study, laboratory-bred specimens of Musca domestica were infected by feeding on anthrax-infected rabbit carcass or anthrax contaminated blood, and the presence of anthrax spores in their spots (faeces and vomitus was microbiologically monitored. It was also evaluated if the anthrax spores were able to germinate and replicate in the gut content of insects. These results confirmed the role of insects in spreading anthrax infection. This role, although not major, given the huge size of fly populations often associated with anthrax epidemics in domestic animals, cannot be neglected from an epidemiological point of view and suggest that fly control should be considered as part of anthrax control programs.

  1. Proteomics Reveals that Proteins Expressed During the Early Stage of Bacillus anthracis Infection Are Potential Targets for the Development of Vaccines and Drugs

    Institute of Scientific and Technical Information of China (English)

    Chun-Ming Huang; Craig A. Elmets; De-chu C. Tang; Fuming Li; Nabiha Yusuf

    2004-01-01

    In this review, we advance a new concept in developing vaccines and/or drugs to target specific proteins expressed during the early stage of Bacillus anthracis (an thrax) infection and address existing challenges to this concept. Three proteins (immune inhibitor A, GPR-like spore protease, and alanine racemase) initially identified by proteomics in our laboratory were found to have differential expres sions during anthrax spore germination and early outgrowth. Other studies of different bacillus strains indicate that these three proteins are involved in either germination or cytotoxicity of spores, suggesting that they may serve as potential targets for the design of anti-anthrax vaccines and drugs.

  2. Cytoskeleton as an Emerging Target of Anthrax Toxins

    Directory of Open Access Journals (Sweden)

    Jean-Nicolas Tournier

    2012-02-01

    Full Text Available Bacillus anthracis, the agent of anthrax, has gained virulence through its exotoxins produced by vegetative bacilli and is composed of three components forming lethal toxin (LT and edema toxin (ET. So far, little is known about the effects of these toxins on the eukaryotic cytoskeleton. Here, we provide an overview on the general effects of toxin upon the cytoskeleton architecture. Thus, we shall discuss how anthrax toxins interact with their receptors and may disrupt the interface between extracellular matrix and the cytoskeleton. We then analyze what toxin molecular effects on cytoskeleton have been described, before discussing how the cytoskeleton may help the pathogen to corrupt general cell processes such as phagocytosis or vascular integrity.

  3. Economic Impacts of a Wide Area Release of Anthrax

    Energy Technology Data Exchange (ETDEWEB)

    Judd, Kathleen S.; Olson, Jarrod; Stein, Steven L.; Lesperance, Ann M.

    2009-05-29

    This analysis explores economic impacts that might result from a wide-area release of anthrax. The intent is not to provide a quantitative analysis of such a disaster, but to: 1. Define the general categories of economic impacts that the region should be concerned about; and, 2. Explore what types of private sector businesses or industries, if any, may have the greatest impact on speeding the economic recovery of the region.

  4. Effective antiprotease-antibiotic treatment of experimental anthrax

    Directory of Open Access Journals (Sweden)

    MacAfee Rebecca

    2005-04-01

    Full Text Available Abstract Background Inhalation anthrax is characterized by a systemic spread of the challenge agent, Bacillus anthracis. It causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. It is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of intoxication in experimental animals is drastically different from that found during the infectious process. In order to close a gap between our understanding of anthrax molecular pathology and the most prominent clinical features of the infectious process we undertook bioinformatic and experimental analyses of potential proteolytic virulence factors of B. anthracis distinct from lethal toxin. Methods Secreted proteins (other than lethal and edema toxins produced by B. anthracis were tested for tissue-damaging activity and toxicity in mice. Chemical protease inhibitors and rabbit immune sera raised against B. anthracis proteases were used to treat mice challenged with B. anthracis (Sterne spores. Results B. anthracis strain delta Ames (pXO1-, pXO2- producing no lethal and edema toxins secrets a number of metalloprotease virulence factors upon cultivation under aerobic conditions, including those with hemorrhagic, caseinolytic and collagenolytic activities, belonging to M4 and M9 thermolysin and bacterial collagenase families, respectively. These factors are directly toxic to DBA/2 mice upon intratracheal administration at 0.5 mg/kg and higher doses. Chemical protease inhibitors (phosphoramidon and 1, 10-phenanthroline, as well as immune sera against M4 and M9 proteases of B. anthracis, were used to treat mice challenged with B. anthracis (Sterne spores. These substances demonstrate a substantial protective efficacy in combination with ciprofloxacin therapy initiated as late as 48 h post spore challenge, compared to the antibiotic alone. Conclusion Secreted proteolytic enzymes are important pathogenic

  5. Anthrax kills wild chimpanzees in a tropical rainforest.

    Science.gov (United States)

    Leendertz, Fabian H; Ellerbrok, Heinz; Boesch, Christophe; Couacy-Hymann, Emmanuel; Mätz-Rensing, Kerstin; Hakenbeck, Regine; Bergmann, Carina; Abaza, Pola; Junglen, Sandra; Moebius, Yasmin; Vigilant, Linda; Formenty, Pierre; Pauli, Georg

    2004-07-22

    Infectious disease has joined habitat loss and hunting as threats to the survival of the remaining wild populations of great apes. Nevertheless, relatively little is known about the causative agents. We investigated an unusually high number of sudden deaths observed over nine months in three communities of wild chimpanzees (Pan troglodytes verus) in the Taï National Park, Ivory Coast. Here we report combined pathological, cytological and molecular investigations that identified Bacillus anthracis as the cause of death for at least six individuals. We show that anthrax can be found in wild non-human primates living in a tropical rainforest, a habitat not previously known to harbour B. anthracis. Anthrax is an acute disease that infects ruminants, but other mammals, including humans, can be infected through contacting or inhaling high doses of spores or by consuming meat from infected animals. Respiratory and gastrointestinal anthrax are characterized by rapid onset, fever, septicaemia and a high fatality rate without early antibiotic treatment. Our results suggest that epidemic diseases represent substantial threats to wild ape populations, and through bushmeat consumption also pose a hazard to human health.

  6. Injectional anthrax at a Scottish district general hospital.

    Science.gov (United States)

    Inverarity, D J; Forrester, V M; Cumming, J G R; Paterson, P J; Campbell, R J; Brooks, T J G; Carson, G L; Ruddy, J P

    2015-04-01

    This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

  7. Human Anthrax Transmission at the Urban-Rural Interface, Georgia.

    Science.gov (United States)

    Kracalik, Ian; Malania, Lile; Imnadze, Paata; Blackburn, Jason K

    2015-12-01

    Human anthrax has increased dramatically in Georgia and was recently linked to the sale of meat in an urban market. We assessed epidemiological trends and risk factors for human anthrax at the urban-rural interface. We reviewed epidemiologic records (2000-2012) that included the place of residence (classified as urban, peri-urban, or rural), age, gender, and self-reported source of infection (handling or processing animal by-products and slaughtering or butchering livestock). To estimate risk, we used a negative binomial regression. The average incidence per 1 million population in peri-urban areas (24.5 cases) was > 2-fold higher compared with rural areas and > 3-fold higher compared with urban area. Risk from handling or purchasing meat was nearly 2-fold higher in urban areas and > 4-fold higher in peri-urban areas compared with rural area. Our findings suggest a high risk of anthrax in urban and peri-urban areas likely as a result of spillover from contaminated meat and animal by-products. Consumers should be warned to purchase meat only from licensed merchants.

  8. Interactions between Bacillus anthracis and plants may promote anthrax transmission.

    Directory of Open Access Journals (Sweden)

    Holly H Ganz

    2014-06-01

    Full Text Available Environmental reservoirs are essential in the maintenance and transmission of anthrax but are poorly characterized. The anthrax agent, Bacillus anthracis was long considered an obligate pathogen that is dormant and passively transmitted in the environment. However, a growing number of laboratory studies indicate that, like some of its close relatives, B. anthracis has some activity outside of its vertebrate hosts. Here we show in the field that B. anthracis has significant interactions with a grass that could promote anthrax spore transmission to grazing hosts. Using a local, virulent strain of B. anthracis, we performed a field experiment in an enclosure within a grassland savanna. We found that B. anthracis increased the rate of establishment of a native grass (Enneapogon desvauxii by 50% and that grass seeds exposed to blood reached heights that were 45% taller than controls. Further we detected significant effects of E. desvauxii, B. anthracis, and their interaction on soil bacterial taxa richness and community composition. We did not find any evidence for multiplication or increased longevity of B. anthracis in bulk soil associated with grass compared to controls. Instead interactions between B. anthracis and plants may result in increased host grazing and subsequently increased transmission to hosts.

  9. A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective Antigen

    Science.gov (United States)

    2014-08-01

    A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective Antigen...A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective Antigen...AND SUBTITLE A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective

  10. 9 CFR 309.7 - Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and driveways.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Livestock affected with anthrax... INSPECTION § 309.7 Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and driveways. (a) Any livestock found on ante-mortem inspection to be affected with anthrax shall be...

  11. [Bacterial spore--a new vaccine vehicle--a review].

    Science.gov (United States)

    Wang, Yanchun; Zhang, Zhaoshan

    2008-03-01

    Bacterial spores are robust and dormant life forms with formidable resistance properties. Spores of the genus Bacillus have been used for a long time as probiotics for oral bacteriotherapy both in humans and animals. Recently, genetically modified B. subtilis spores and B. anthracis spores have been used as indestructible delivery vehicles for vaccine antigens. They were used as vaccine vehicles or spore vaccine for oral immunization against tetanus and anthrax, and the results were very exciting. Unlike many second generation vaccine systems currently under development, bacterial spores offer heat stability and the flexibility for genetic manipulation. At the same time, they can elicit mucosal immune response by oral and nasal administration. This review focuses on the use of recombinant spores as vaccine delivery vehicles.

  12. Case Report of an Anthrax Presentation Relevant to Special Operations Medicine.

    Science.gov (United States)

    Winkler, Stephen; Enzenauer, Robert W; Karesh, James W; Pasteur, Nshimyimana; Eisnor, Derek L; Painter, Rex B; Calvano, Christopher J

    2016-01-01

    Special Operations Forces (SOF) medical personnel function worldwide in environments where endemic anthrax (caused by Bacillus anthracis infection) may present in one of three forms: cutaneous, pulmonary, or gastrointestinal. This report presents a rare periocular anthrax case from Haiti to emphasize the need for heightened diagnostic suspicion of unusual lesions likely to be encountered in SOF theaters.

  13. Anthrax toxins cooperatively inhibit endocytic recycling by the Rab11/Sec15 exocyst

    NARCIS (Netherlands)

    Guichard, Annabel; McGillivray, Shauna M.; Cruz-Moreno, Beatriz; van Sorge, Nina M.; Nizet, Victor; Bier, Ethan

    2010-01-01

    Bacillus anthracis is the causative agent of anthrax in humans and other mammals(1,2). In lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (LF) and oedema factor (EF), leading to widespread vascular leakage and shock. Whereas host targets of LF (mit

  14. Use of medical simulation to teach bioterrorism preparedness: the anthrax example.

    Science.gov (United States)

    Olsen, Martin E

    2013-01-01

    The 2001 anthrax bioterrorism attacks demonstrated vulnerability for future similar attacks. This article describes mechanisms that can be used to prepare the medical community and healthcare facilities for the diagnosis and management of a subsequent bioterrorism attack should such an event occur and the fundamentals of medical simulation and its use in teaching learners about the diagnosis of management of anthrax exposure.

  15. Awareness and attitude toward zoonoses with particular reference to anthrax among cattle owners in selected rural communities of Zimbabwe.

    Science.gov (United States)

    Chikerema, S M; Matope, G; Pfukenyi, D M

    2013-04-01

    We conducted a cross-sectional study to assess cattle owners' awareness, perceptions, and attitudes toward zoonoses, with particular emphasis regarding anthrax. Data on awareness of zoonoses, clinical signs of anthrax in animals and human, its routes of transmission and methods of prevention, the families' consumption habits of anthrax-infected carcasses, and other family activities that increase exposure to anthrax were collected using an interviewer-administered questionnaire. A total of 41.4% (135/326) of the farmers were from high-anthrax-risk districts, whereas 28.5% and 30.1% were from medium- and low-risk districts, respectively. Overall, the level of awareness amongst the farmers for the named zoonoses were rabies (88.7%), anthrax (71.5%), and brucellosis (20.9%). Except for anthrax, awareness of other zoonoses did not differ significantly (p>0.05) among the district categories. Farmers from anthrax high-risk districts were significantly more aware of anthrax compared to those from moderate- (p=0.000) and low- (p=0.000) risk districts. All of the farmers were aware that anthrax occurs in cattle, and 73% indicated the presence of unclotting blood oozing from natural orifices as a consistent finding in cattle that died of anthrax, whereas 86.7% of them indicated the presence of skin lesions as the most common sign of the disease in humans. The good efficacy of human anthrax treatment (58.3%), slaughter of moribund cattle and selling of meat from cattle found dead to unsuspecting consumers (59.8%), reluctance to lose animals (47.9%), and forgetting about anthrax (41.1%) were cited as the major reasons for consuming anthrax-infected carcasses. Given that 75.2% of cattle owners indicated that they would not consume meat from cattle found dead, because they were discouraged by veterinary authorities, introducing meat inspection services is likely to have a positive impact in preventing human anthrax outbreaks in Zimbabwe.

  16. Keeping the Air Clean and Safe: An Anthrax Smoke Detector

    Science.gov (United States)

    2005-01-01

    Scientists at work in the Planetary Protection division at NASA s Jet Propulsion Laboratory (JPL) sterilize everything before blasting it to the Red Planet. They take great pains to ensure that all spacecraft are void of bacterial life, especially the microscopic bacteria that can live hundreds of years in their spore states. No one is quite sure what Earthly germs would do on Mars, but scientists agree that it is safest to keep the Martian terrain as undisturbed as possible. Errant Earth germs would also render useless the instruments placed on exploration rovers to look for signs of life, as the life that they registered would be life that came with them from Earth. A team at JPL, headed by Dr. Adrian Ponce, developed a bacterial spore-detection system that uses a simple and robust chemical reaction that visually alerts Planetary Protection crews. It is a simple air filter that traps micron-sized bacterial spores and then submits them to the chemical reaction. When the solution is then viewed under an ultraviolet light, the mixture will glow green if it is contaminated by bacteria. Scientists can then return to the scrubbing and cleaning stages of the sterilization process to remove these harmful bacteria. The detection system is the space-bound equivalent of having your hands checked for cleanliness before being allowed to the table; and although intended to keep terrestrial germs from space, this technology has awesome applications here on Mother Earth. The bacterial spore-detection unit can recognize anthrax and other harmful, spore-forming bacteria and alert people of the impending danger. As evidenced in the anthrax mailings of fall 2001 in the United States, the first sign of anthrax exposure was when people experienced flu-like symptoms, which unfortunately, can take as much as a week to develop after contamination. Anthrax cost 5 people their lives and infected 19 others; and the threat of bioterrorism became a routine concern, with new threats popping up

  17. Anthrax in a backyard domestic dog in Ukraine: a case report.

    Science.gov (United States)

    Blackburn, Jason K; Skrypnyk, Artem; Bagamian, Karoun H; Nikolich, Mikeljon P; Bezymennyi, Maksym; Skrypnyk, Valeriy

    2014-08-01

    Anthrax has been reported in domestic and wild dogs throughout much of the world. Generally, canids are considered resistant to anthrax, although there are several reports of anthrax deaths in both wild and domestic canid populations. Prior to 2012, anthrax had not been reported in dogs in Ukraine, despite a long history in livestock and wildlife. An outbreak involving at least one cow and one dog was reported from a backyard setting in southern Ukraine in August of 2012. Laboratory results and epizootic data were compiled from official investigation reports of regional and state veterinary services involved in the case response. A single dog died after being fed meat and bones from an illegally slaughtered heifer that died of anthrax 5 days earlier. On the evening of the dog's death, the dog refused food or water; however, there were no other clinical signs. Laboratory tests of dog tissue included traditional bacteriology for Bacillus anthracis, a small rodent bioassay for virulence, and immunoprecipitation tests (IPT). IPT was positive, viable B. anthracis colonies were cultured, and a bioassay confirmed virulence. This was the first confirmed case of canid anthrax in Ukraine. This case report serves to remind veterinary officials that anthrax can affect a wide number of species. We advise surveillance systems remain flexible and include animals that might not otherwise be tested.

  18. The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax.

    Science.gov (United States)

    Coggeshall, Kenneth Mark; Lupu, Florea; Ballard, Jimmy; Metcalf, Jordan P; James, Judith A; Farris, Darise; Kurosawa, Shinichiro

    2013-07-01

    Inhalation anthrax is often described as a toxin-mediated disease. However, the toxaemia model does not account for the high mortality of inhalation anthrax relative to other forms of the disease or for the pathology present in inhalation anthrax. Patients with inhalation anthrax consistently show extreme bacteraemia and, in contrast to animals challenged with toxin, signs of sepsis. Rather than toxaemia, we propose that death in inhalation anthrax results from an overwhelming bacteraemia that leads to severe sepsis. According to our model, the central role of anthrax toxin is to permit the vegetative bacteria to escape immune detection. Other forms of B. anthracis infection have lower mortality because their overt symptoms early in the course of disease cause patients to seek medical care at a time when the infection and its sequelae can still be reversed by antibiotics. Thus, the sepsis model explains key features of inhalation anthrax and may offer a more complete understanding of disease pathology for researchers as well as those involved in the care of patients.

  19. Surveillance and control of anthrax and rabies in wild herbivores and carnivores in Namibia.

    Science.gov (United States)

    Berry, H H

    1993-03-01

    Anthrax has been studied intensively in Etosha National Park, Namibia since 1966; in addition, since 1975, mortality due to rabies and all other causes has been recorded, totalling 6,190 deaths. Standard diagnostic procedures demonstrated that at least 811 deaths (13%) were due to anthrax and 115 deaths (2%) were caused by rabies. Of the total number of deaths due to anthrax, 97% occurred in zebra (Equus burchelli), elephant (Loxodonta africana), wildebeest (Connochaetes taurinus) and springbok (Antidorcas marsupialis) while 96% of rabies deaths occurred in kudu (Tragelaphus strepsiceros), jackal (Canis mesomelas), bat-eared fox (Otocyon megalotis) and lion (Panthera leo). Anthrax deaths were highest in the rainy season for zebra, wildebeest and springbok, while elephant mortality peaked during dry seasons. No statistical relationship existed between seasonal rainfall and overall incidence of either anthrax or rabies. Control of anthrax is limited to prophylactic inoculation when rare or endangered species are threatened. Incineration of anthrax carcasses and chemical disinfection of drinking water are not feasible at Etosha. Rabies control consists of the destruction of rabid animals and incineration of their carcasses when possible.

  20. Detection of anthrax toxin genetic sequences by the solid phase oligo-probes

    Directory of Open Access Journals (Sweden)

    K C Addanki

    2011-01-01

    Full Text Available Purpose: There is an urgent need to detect a rapid field-based test to detect anthrax. We have developed a rapid, highly sensitive DNA-based method to detect the anthrax toxin lethal factor gene located in pXO1, which is necessary for the pathogenicity of Bacillus anthracis. Materials and Methods: We have adopted the enzyme-linked immunosorbent assay (ELISA so that instead of capturing antibodies we capture the DNA of the target sequence by a rapid oligo-based hybridization and then detect the captured DNA with another oligoprobe that binds to a different motif of the captured DNA sequences at a dissimilar location. We chose anthrax lethal factor endopeptidase sequences located in pXO1 and used complementary oligoprobe, conjugated with biotin, to detect the captured anthrax specific sequence by the streptavidin-peroxidase-based colorimetric assay. Result: Our system can detect picomoles (pMoles of anthrax (approximately 33 spores of anthrax and is >1000 times more sensitive than the current ELISA, which has a detection range of 0.1 to 1.0 ng/mL. False positive results can be minimized when various parameters and the colour development steps are optimized. Conclusion: Our results suggest that this assay can be adapted for the rapid detection of minuscule amounts of the anthrax spores that are aerosolized in the case of a bioterrorism attack. This detection system does not require polymerase chain reaction (PCR step and can be more specific than the antibody method. This method can also detect genetically engineered anthrax. Since, the antibody method is so specific to the protein epitope that bioengineered versions of anthrax may not be detected.

  1. Surface plasmon resonance measurements of plasma antibody avidity during primary and secondary responses to anthrax protective antigen.

    Science.gov (United States)

    Lynch, Heather E; Stewart, Shelley M; Kepler, Thomas B; Sempowski, Gregory D; Alam, S Munir

    2014-02-01

    Establishment of humoral immunity against pathogens is dependent on events that occur in the germinal center and the subsequent induction of high-affinity neutralizing antibodies. Quantitative assays that allow monitoring of affinity maturation and duration of antibody responses can provide useful information regarding the efficacy of vaccines and adjuvants. Using an anthrax protective antigen (rPA) and alum model antigen/adjuvant system, we describe a methodology for monitoring antigen-specific serum antibody concentration and avidity by surface plasmon resonance during primary and secondary immune responses. Our analyses showed that following a priming dose in mice, rPA-specific antibody concentration and avidity increases over time and reaches a maximal response in about six weeks, but gradually declines in the absence of antigenic boost. Germinal center reactions were observed early with maximal development achieved during the primary response, which coincided with peak antibody avidity responses to primary immunization. Boosting with antigen resulted in a rapid increase in rPA-specific antibody concentration and five-fold increase in avidity, which was not dependent on sustained GC development. The described methodology couples surface plasmon resonance-based plasma avidity measurements with germinal center analysis and provides a novel way to monitor humoral responses that can play a role in facilitating vaccine and adjuvant development.

  2. [Travelers' vaccines].

    Science.gov (United States)

    Ouchi, Kazunobu

    2011-09-01

    The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.

  3. [Characteristics of anthrax: its description and biblical name--Shehin].

    Science.gov (United States)

    Ben-Noun, Liubov

    2002-05-01

    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.

  4. Epidemiology of Human Anthrax in China, 1955−2014

    Science.gov (United States)

    Li, Yu; Yin, Wenwu; Hugh-Jones, Martin; Wang, Liping; Mu, Di; Ren, Xiang; Zeng, Lingjia; Chen, Qiulan; Li, Wei; Wei, Jianchun; Lai, Shengjie; Zhou, Hang

    2017-01-01

    Using national surveillance data for 120,111 human anthrax cases recorded during 1955−2014, we analyzed the temporal, seasonal, geographic, and demographic distribution of this disease in China. After 1978, incidence decreased until 2013, when it reached a low of 0.014 cases/100,000 population. The case-fatality rate, cumulatively 3.6% during the study period, has also decreased since 1990. Cases occurred throughout the year, peaking in August. Geographic distribution decreased overall from west to east, but the cumulative number of affected counties increased during 2005−2014. The disease has shifted from industrial to agricultural workers; 86.7% of cases occurred in farmers and herdsmen. Most (97.7%) reported cases were the cutaneous form. Although progress has been made in reducing incidence, this study highlights areas that need improvement. Adequate laboratory diagnosis is lacking; only 7.6% of cases received laboratory confirmation. Geographic expansion of the disease indicates that livestock control programs will be essential in eradicating anthrax. PMID:27983489

  5. Suppressive effects of anthrax lethal toxin on megakaryopoiesis.

    Directory of Open Access Journals (Sweden)

    Po-Kong Chen

    Full Text Available Anthrax lethal toxin (LT is a major virulence factor of Bacillus anthracis. LT challenge suppresses platelet counts and platelet function in mice, however, the mechanism responsible for thrombocytopenia remains unclear. LT inhibits cellular mitogen-activated protein kinases (MAPKs, which are vital pathways responsible for cell survival, differentiation, and maturation. One of the MAPKs, the MEK1/2-extracellular signal-regulated kinase pathway, is particularly important in megakaryopoiesis. This study evaluates the hypothesis that LT may suppress the progenitor cells of platelets, thereby inducing thrombocytopenic responses. Using cord blood-derived CD34(+ cells and mouse bone marrow mononuclear cells to perform in vitro differentiation, this work shows that LT suppresses megakaryopoiesis by reducing the survival of megakaryocytes. Thrombopoietin treatments can reduce thrombocytopenia, megakaryocytic suppression, and the quick onset of lethality in LT-challenged mice. These results suggest that megakaryocytic suppression is one of the mechanisms by which LT induces thrombocytopenia. These findings may provide new insights for developing feasible approaches against anthrax.

  6. Antimicrobial Treatment for Systemic Anthrax: Analysis of Cases from 1945 to 2014 Identified Through a Systematic Literature Review.

    Science.gov (United States)

    Pillai, Satish K; Huang, Eileen; Guarnizo, Julie T; Hoyle, Jamechia D; Katharios-Lanwermeyer, Stefan; Turski, Theresa K; Bower, William A; Hendricks, Katherine A; Meaney-Delman, Dana

    2015-01-01

    Systemic anthrax is associated with high mortality. Current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of 2 weeks, bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax, and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. However, in an anthrax mass casualty incident, large numbers of anthrax cases may create challenges in meeting antimicrobial needs. To further inform our understanding of the role of antimicrobials in treating systemic anthrax, a systematic review of the English-language literature was conducted to identify cases of systemic anthrax treated with antimicrobials for which a clinical outcome was recorded. A total of 149 cases of systemic anthrax were identified. Among the identified 59 cases of cutaneous anthrax, 33 were complicated by meningitis (76% mortality), while 26 simply had evidence of the systemic inflammatory response syndrome (4% mortality); 21 of 26 (81%) of this latter group received monotherapy. Subsequent analysis regarding combination antimicrobial therapy was restricted to the remaining 123 cases of more severe anthrax (overall 67% mortality). Recipients of combination bactericidal and protein synthesis inhibitor therapy had a 45% survival versus 28% in the absence of combination therapy (p = 0.07). For meningitis cases (n = 77), survival was greater for those receiving 3 or more antimicrobials over the course of treatment (3 of 4; 75%), compared to receipt of 1 or 2 antimicrobials (12 of 73; 16%) (p = 0.02). Median parenteral antimicrobial duration was 14 days. Combination bactericidal and protein synthesis inhibitor therapy may be appropriate in severe anthrax disease, particularly anthrax meningitis, in a mass casualty incident.

  7. Leptospirosis vaccines

    Directory of Open Access Journals (Sweden)

    Jin Li

    2007-12-01

    Full Text Available Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP vaccines, lipopolysaccharide (LPS vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.

  8. Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years

    Directory of Open Access Journals (Sweden)

    Paul Keim

    2015-11-01

    Lay Person Interpretation: Injectional anthrax has been plaguing heroin drug users across Europe for more than 10 years. In order to better understand this outbreak, we assessed genomic relationships of all available injectional anthrax strains from four countries spanning a >12 year period. Very few differences were identified using genome-based analysis, but these differentiated the isolates into two distinct clusters. This strongly supports a hypothesis of at least two separate anthrax spore contamination events perhaps during the drug production processes. Identification of two events would not have been possible from standard epidemiological analysis. These comprehensive data will be invaluable for classifying future injectional anthrax isolates and for future geographic attribution.

  9. Targeting the inflammasome and adenosine type-3 receptors improves outcome of antibiotic therapy in murine anthrax

    OpenAIRE

    Popov, Serguei G.; Popova, Taissia G.; Kashanchi, Fatah; Bailey, Charles

    2011-01-01

    AIM: To establish whether activation of adenosine type-3 receptors (A3Rs) and inhibition of interleukin-1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores.

  10. Anthrax in injecting drug users: the need for increased vigilance in the clinic.

    Science.gov (United States)

    Ascough, Stephanie; Altmann, Daniel Martin

    2015-06-01

    The emergence of a previously unrecognized route of Bacillus anthracis infection over the last few years has led to concern: sporadic anthrax outbreaks among heroin users in northern Europe have demonstrated the severe pathology associated with the newly described 'injectional anthrax'. With a high case fatality rate and non-specific early symptoms, this is a novel clinical manifestation of an old disease. Lack of awareness of this syndrome among emergency room clinicians can lead to a delayed diagnosis among heroin users; indeed, for many health workers in developed countries, where infection by B. anthracis is rare, this may be the first time they have encountered anthrax infections. As the putative route of contamination of the heroin supply is potentially ongoing, it is important that clinicians and public health workers remain vigilant for early signs of injectional anthrax.

  11. Vaccine Hesitancy.

    Science.gov (United States)

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact.

  12. Lessons for control of heroin-associated anthrax in Europe from 2009-2010 outbreak case studies, London, UK.

    Science.gov (United States)

    Abbara, Aula; Brooks, Tim; Taylor, Graham P; Nolan, Marianne; Donaldson, Hugo; Manikon, Maribel; Holmes, Alison

    2014-07-01

    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.

  13. Animal models of human anthrax: the Quest for the Holy Grail.

    Science.gov (United States)

    Goossens, Pierre L

    2009-12-01

    Anthrax is rare among humans, few data can be collected from infected individuals and they provide a fragmentary view of the dynamics of infection and human host-pathogen interactions. Therefore, the development of animal models is necessary. Anthrax has the particularity of being a toxi-infection, a combination of infection and toxemia. The ideal animal model would explore these two different facets and mimic human disease as much as possible. In the past decades, the main effort has been focused on modelling of inhalational anthrax and the perception of specific aspects of the infection has evolved in recent years. In this review, we consider criteria which can lead to the most appropriate choice of a given animal species for modelling human anthrax. We will highlight the positive input and limitations of different models and show that they are not mutually exclusive. On the contrary, their contribution to anthrax research can be more rewarding when taken in synergy. We will also present a reappraisal of inhalational anthrax and propose reflections on key points, such as portal of entry, connections between mediastinal lymph nodes, pleura and lymphatic drainage.

  14. Passive Immunotherapy Protects against Enteric Invasion and Lethal Sepsis in a Murine Model of Gastrointestinal Anthrax.

    Science.gov (United States)

    Huang, Bruce; Xie, Tao; Rotstein, David; Fang, Hui; Frucht, David M

    2015-09-29

    The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay.

  15. Prediction of Protein-Peptide Interactions: Application of the XPairIT to Anthrax Lethal Factor and Substrates

    Science.gov (United States)

    2013-09-01

    Prediction of Protein-Peptide Interactions: Application of the XPairIt API to Anthrax Lethal Factor and Substrates by Margaret M. Hurley and...Peptide Interactions: Application of the XPairIt API to Anthrax Lethal Factor and Substrates Margaret M. Hurley and Michael S. Sellers Weapons and...Prediction of Protein-Peptide Interactions: Application of the XPairIt API to Anthrax Lethal Factor and Substrates 5a. CONTRACT NUMBER ORAUW911QX-04-C

  16. In silico design of smart binders to anthrax PA

    Science.gov (United States)

    Sellers, Michael; Hurley, Margaret M.

    2012-06-01

    The development of smart peptide binders requires an understanding of the fundamental mechanisms of recognition which has remained an elusive grail of the research community for decades. Recent advances in automated discovery and synthetic library science provide a wealth of information to probe fundamental details of binding and facilitate the development of improved models for a priori prediction of affinity and specificity. Here we present the modeling portion of an iterative experimental/computational study to produce high affinity peptide binders to the Protective Antigen (PA) of Bacillus anthracis. The result is a general usage, HPC-oriented, python-based toolkit based upon powerful third-party freeware, which is designed to provide a better understanding of peptide-protein interactions and ultimately predict and measure new smart peptide binder candidates. We present an improved simulation protocol with flexible peptide docking to the Anthrax Protective Antigen, reported within the context of experimental data presented in a companion work.

  17. 1958-2010年阿坝州炭疽流行状况分析%Prevalence of Anthrax in Aba Prefecture, 1958 -2010

    Institute of Scientific and Technical Information of China (English)

    敬琼

    2012-01-01

    目的 分析阿坝州1958 -2010年炭疽发病情况,找出发病规律和特点,探讨有效降低炭疽病发病的措施和方法.方法 对53年来的炭疽疫情数据进行流行病学分析.结果 53年来累计报告炭疽病例1 349例,死亡21例,年均发病率3.47/10万、死亡率0.06/10万.全年均有病例报告,但集中在4~10月,3个牧区县的发病占报告总数的89.03%;职业以牧民为主,发病年龄集中在20~44岁.1958 - 2001年发病率在0.8/10万~2.52/10万之间,2002-2010年发病率在6.33/10万~12.66/10万之间.结论 阿坝州1958 -2001年炭疽发病较平稳,2002年起发病呈逐年上升趋势,且发病主要在牧区,应加强健康教育和畜牧业管理,做好疫点、外环境消毒和预防接种,有效控制牧区炭疽流行.%Objective By analyzing the incidence of anthrax in Aba prefecture from year 1958 to 2010, to find out the rules and features of the incidence, and explore effective measures to reduce the incidence of anthrax. Methods Data of anthrax epidemics in 53 years (1958 -2010) was analyzed with epidemiological methods. Results Totally 1 349 anthrax cases were reported in 53 years, with 21 death cases. The annual incidence rate was 3.47/105, and case mortality rate was 0. 06/105. Cases were reported throughout the year, and concentrated in period of April to October, 89. 03% cases were from 3 pastoral counties. Professional was mainly pas-toralists, and cases concentrated in 20 -44 years old. Annual incidence rate during 1958 -2001 fluctuated within 0. 8/105 -2. 52/105, and annual incidence rate was from 6. 33/105 to 12. 66/105 during 2002 -2010. Conclusions The incidence of anthrax was stable in Aba prefecture during 1958 - 2001, followed by the in- , creasing since 2002 year by year, and mainly in pastoral areas. Health education and animal husbandry management should be strengthened, with epidemic focus and external environment disinfection and vaccination, to control the prevalence of

  18. Monitoring Method of Cow Anthrax Based on Gis and Spatial Statistical Analysis

    Science.gov (United States)

    Li, Lin; Yang, Yong; Wang, Hongbin; Dong, Jing; Zhao, Yujun; He, Jianbin; Fan, Honggang

    Geographic information system (GIS) is a computer application system, which possesses the ability of manipulating spatial information and has been used in many fields related with the spatial information management. Many methods and models have been established for analyzing animal diseases distribution models and temporal-spatial transmission models. Great benefits have been gained from the application of GIS in animal disease epidemiology. GIS is now a very important tool in animal disease epidemiological research. Spatial analysis function of GIS can be widened and strengthened by using spatial statistical analysis, allowing for the deeper exploration, analysis, manipulation and interpretation of spatial pattern and spatial correlation of the animal disease. In this paper, we analyzed the cow anthrax spatial distribution characteristics in the target district A (due to the secret of epidemic data we call it district A) based on the established GIS of the cow anthrax in this district in combination of spatial statistical analysis and GIS. The Cow anthrax is biogeochemical disease, and its geographical distribution is related closely to the environmental factors of habitats and has some spatial characteristics, and therefore the correct analysis of the spatial distribution of anthrax cow for monitoring and the prevention and control of anthrax has a very important role. However, the application of classic statistical methods in some areas is very difficult because of the pastoral nomadic context. The high mobility of livestock and the lack of enough suitable sampling for the some of the difficulties in monitoring currently make it nearly impossible to apply rigorous random sampling methods. It is thus necessary to develop an alternative sampling method, which could overcome the lack of sampling and meet the requirements for randomness. The GIS computer application software ArcGIS9.1 was used to overcome the lack of data of sampling sites.Using ArcGIS 9.1 and GEODA

  19. Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.

    Science.gov (United States)

    Ascough, Stephanie; Ingram, Rebecca J; Chu, Karen K; Reynolds, Catherine J; Musson, Julie A; Doganay, Mehmet; Metan, Gökhan; Ozkul, Yusuf; Baillie, Les; Sriskandan, Shiranee; Moore, Stephen J; Gallagher, Theresa B; Dyson, Hugh; Williamson, E Diane; Robinson, John H; Maillere, Bernard; Boyton, Rosemary J; Altmann, Daniel M

    2014-05-01

    Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

  20. Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.

    Directory of Open Access Journals (Sweden)

    Stephanie Ascough

    2014-05-01

    Full Text Available Bacillus anthracis produces a binary toxin composed of protective antigen (PA and one of two subunits, lethal factor (LF or edema factor (EF. Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

  1. Vaccines against biologic agents: uses and developments.

    Science.gov (United States)

    Ales, Noel C; Katial, Rohit K

    2004-03-01

    concentrations of organisms may overcome vaccine protection. Finally,exposure may not be immediately noted until it is too late to vaccinate, as was the case with anthrax. Even in a case, such as smallpox, in which postexposure vaccination is possible, patients will still develop disease, and the health care system may be overwhelmed. The United States government has been defensively planning and researching the use of vaccines and chemoprophylaxis against any potential biologic agents since at least 1953, and resources are still lacking. There are inadequate stockpiles of vaccine to protect the entire population. The pharmaceutical industry also lacks a means of mass producing vaccines ina short timeframe. There is no policy in place for the use of vaccines that are yet unlicensed and experimental but may be the only therapy in the event ofa terrorist attack. Investigations into these solutions have been instituted only after the September 11, 2001, attacks heightened the awareness of terrorism. Although vaccination is an effective means of prophylaxis and a means of terminating epidemics or treating active disease, there is also resistance from the general public. In some instances there is a lack of acceptance of vaccines, or the risk of side effects is too great. In other cases, a questionable benefit does not justify the expense of mass vaccination. Because of this uncertainty, mass vaccination is deemed an impractical solution to the threat of bioterrorism. Extending vaccination with most vaccines to include all members of society who may be first responders in the event of an attack should be considered. In all instances, the benefit-to-risk must be weighed ratio when deciding how and when to offer preemptive prophylaxis to protect society from a real but unknown threat.

  2. A One Health, participatory epidemiology assessment of anthrax (Bacillus anthracis) management in Western Uganda.

    Science.gov (United States)

    Coffin, Jeanne L; Monje, Fred; Asiimwe-Karimu, Grace; Amuguni, Hellen Janetrix; Odoch, Terence

    2015-03-01

    Sporadic anthrax outbreaks have occurred in and around Uganda's Queen Elizabeth National Park (QENP) for years, affecting wildlife, domestic animals, and humans. Reported outbreaks (2004-2005 and 2010) in QENP collectively killed over 500 wild animals and over 400 domestic animals. A 2011 outbreak in Sheema district temporarily froze local markets while killing two humans and seven bovines. One Health is multidisciplinary at its core, yet studies sometimes focus on the effects of animals on human health to the detriment of investigating the surrounding ecological and cultural contexts. Participatory methods connect problems - such as disease - to their context. A multidisciplinary team used participatory epidemiology and conventional structured questionnaires to investigate the impacts of anthrax on human livelihoods and the related perceptions of conservation, public health, and veterinary health efforts in the QENP area. Proximities to previous anthrax outbreaks and to QENP were treated as risk factors in the collection and evaluation of data. Participants' feedback indicates that anthrax prevalence may be greater than officially reported. Community member perceptions about anthrax and other diseases appear to be more closely related to their proximity to QENP than their proximity to anthrax outbreaks. Neither risk factor had a strong effect on knowledge of disease, nor any effect on behaviors associated with disease response or control. Instead, participants reported that social pressures, the economics of poverty, and the lack of health and veterinary infrastructure highly influenced responses to disease. The complex connections between the social needs and the economic context of these communities seem to be undermining current anthrax control and education measures. This livelihood-based decision-making may be unlikely to respond to educational intervention alone. This study provides a strong base for further research and for improvements in effective disease

  3. DENGUE VACCINES.

    Science.gov (United States)

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

    The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection have made dengue vaccine development difficult. Several vaccine candidates are currently being evaluated in clinical studies. The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on the chimeric yellow fever-dengue virus (CYD-TDV), has progressed to Phase 3 efficacy studies. Several other live-attenuated vaccines, as well as subunit, DNA, and purified inactivated vaccine candidates are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and Virus-Like Particles (VLP)-based vaccines are under evaluation in preclinical studies.

  4. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Diane E. [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA (United States); Hoover, Benjamin [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Cloud, Loretta Grey [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Liu, Shihui [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Molinolo, Alfredo A. [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Leppla, Stephen H. [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Bugge, Thomas H., E-mail: thomas.bugge@nih.go [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  5. Tumor endothelium marker-8 based decoys exhibit superiority over capillary morphogenesis protein-2 based decoys as anthrax toxin inhibitors.

    Directory of Open Access Journals (Sweden)

    Chenguang Cai

    Full Text Available Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA, lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8 and capillary morphogenesis protein-2 (CMG2 can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual. Receptor-like agonists, such as the mammalian cell-expressed von Willebrand factor type A (vWA domain of CMG2 (sCMG2, have demonstrated potency against the anthrax toxin. However, the soluble vWA domain of TEM8 (sTEM8 was ruled out as an anthrax toxin inhibitor candidate due to its inferior affinity to PA. In the present study, we report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, which may contribute to their enhanced protective ability in vivo. Our results suggest that receptor decoys based on TEM8 are promising anthrax toxin inhibitors and, together with the pharmacokinetic studies in this report, may contribute to the development of novel anthrax drugs.

  6. 9 CFR 310.9 - Anthrax; carcasses not to be eviscerated; disposition of affected carcasses; hides, hoofs, horns...

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Anthrax; carcasses not to be...-MORTEM INSPECTION § 310.9 Anthrax; carcasses not to be eviscerated; disposition of affected carcasses...; general cleanup and disinfection. (a) Carcasses found before evisceration to be affected with...

  7. Genome Sequence of Historical Bacillus anthracis Strain Tyrol 4675 Isolated from a Bovine Anthrax Case in Austria

    Science.gov (United States)

    Antwerpen, Markus; Wölfel, Roman

    2017-01-01

    ABSTRACT In 1988, an outbreak of anthrax occurred among cattle in the Austrian state of Tyrol. Since then, Austria has been declared anthrax-free. Here, we report the draft genome sequence of one of these last outbreak strains, Bacillus anthracis Tyrol 4675, isolated from a diseased cow. PMID:28280006

  8. Lethal factor and anti-protective antigen IgG levels associated with inhalation anthrax, Minnesota, USA.

    Science.gov (United States)

    Sprenkle, Mark D; Griffith, Jayne; Marinelli, William; Boyer, Anne E; Quinn, Conrad P; Pesik, Nicki T; Hoffmaster, Alex; Keenan, Joseph; Juni, Billie A; Blaney, David D

    2014-02-01

    Bacillus anthracis was identified in a 61-year-old man hospitalized in Minnesota, USA. Cooperation between the hospital and the state health agency enhanced prompt identification of the pathogen. Treatment comprising antimicrobial drugs, anthrax immune globulin, and pleural drainage led to full recovery; however, the role of passive immunization in anthrax treatment requires further evaluation.

  9. Antidotes to anthrax lethal factor intoxication. Part 1: Discovery of potent lethal factor inhibitors with in vivo efficacy.

    Science.gov (United States)

    Jiao, Guan-Sheng; Kim, Seongjin; Moayeri, Mahtab; Cregar-Hernandez, Lynne; McKasson, Linda; Margosiak, Stephen A; Leppla, Stephen H; Johnson, Alan T

    2010-11-15

    Sub-nanomolar small molecule inhibitors of anthrax lethal factor have been identified using SAR and Merck L915 (4) as a model compound. One of these compounds (16) provided 100% protection in a rat lethal toxin model of anthrax disease.

  10. Antibacterial Properties of Visible-Light-Responsive Carbon-Containing Titanium Dioxide Photocatalytic Nanoparticles against Anthrax

    Directory of Open Access Journals (Sweden)

    Der-Shan Sun

    2016-12-01

    Full Text Available The bactericidal activity of conventional titanium dioxide (TiO2 photocatalyst is effective only on irradiation by ultraviolet light, which restricts the applications of TiO2 for use in living environments. Recently, carbon-containing TiO2 nanoparticles [TiO2(C NP] were found to be a visible-light-responsive photocatalyst (VLRP, which displayed significantly enhanced antibacterial properties under visible light illumination. However, whether TiO2(C NPs exert antibacterial properties against Bacillus anthracis remains elusive. Here, we evaluated these VLRP NPs in the reduction of anthrax-induced pathogenesis. Bacteria-killing experiments indicated that a significantly higher proportion (40%–60% of all tested Bacillus species, including B. subtilis, B. cereus, B. thuringiensis, and B. anthracis, were considerably eliminated by TiO2(C NPs. Toxin inactivation analysis further suggested that the TiO2(C NPs efficiently detoxify approximately 90% of tested anthrax lethal toxin, a major virulence factor of anthrax. Notably, macrophage clearance experiments further suggested that, even under suboptimal conditions without considerable bacterial killing, the TiO2(C NP-mediated photocatalysis still exhibited antibacterial properties through the reduction of bacterial resistance against macrophage killing. Our results collectively suggested that TiO2(C NP is a conceptually feasible anti-anthrax material, and the relevant technologies described herein may be useful in the development of new strategies against anthrax.

  11. Rabies Vaccine

    Science.gov (United States)

    ... high risk of exposure to rabies, such as veterinarians, animal handlers, rabies laboratory workers, spelunkers, and rabies biologics production workers should be offered rabies vaccine. The vaccine should also be considered for: (1) ...

  12. Edible vaccines.

    OpenAIRE

    Artnzen, C J

    1997-01-01

    Vaccines were the result of trial and error research until molecular biology and genetic engineering made possible the creation of of many new and improved vaccines. New vaccines need to be inexpensive, easily administered, and capable of being stored and transported without refrigeration; without these characteristics, developing countries find it difficult to adopt vaccination as the central strategy for preventing their most devastating diseases. The authors describe a promising approach t...

  13. Periodontal vaccine

    OpenAIRE

    Ranjan Malhotra; Anoop Kapoor; Vishakha Grover; Aaswin Kaur Tuli

    2011-01-01

    Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of increasing its power to resist or get rid of a disease. Vaccines are generally prophylactic, i.e. they ameliorate the effects of future infection. One such vaccine considered here is the "Periodontal vaccine". Till date, no preventive modality exists for periodontal disease and treatment rendered is palliative. Thus, availability of pe...

  14. Anthrax toxin receptor 2a controls mitotic spindle positioning.

    Science.gov (United States)

    Castanon, I; Abrami, L; Holtzer, L; Heisenberg, C P; van der Goot, F G; González-Gaitán, M

    2013-01-01

    Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis.

  15. Anthrax Sampling and Decontamination: Technology Trade-Offs

    Energy Technology Data Exchange (ETDEWEB)

    Price, Phillip N.; Hamachi, Kristina; McWilliams, Jennifer; Sohn, Michael D.

    2008-09-12

    The goal of this project was to answer the following questions concerning response to a future anthrax release (or suspected release) in a building: 1. Based on past experience, what rules of thumb can be determined concerning: (a) the amount of sampling that may be needed to determine the extent of contamination within a given building; (b) what portions of a building should be sampled; (c) the cost per square foot to decontaminate a given type of building using a given method; (d) the time required to prepare for, and perform, decontamination; (e) the effectiveness of a given decontamination method in a given type of building? 2. Based on past experience, what resources will be spent on evaluating the extent of contamination, performing decontamination, and assessing the effectiveness of the decontamination in abuilding of a given type and size? 3. What are the trade-offs between cost, time, and effectiveness for the various sampling plans, sampling methods, and decontamination methods that have been used in the past?

  16. HPV Vaccine

    Science.gov (United States)

    ... Surgery? A Week of Healthy Breakfasts Shyness HPV Vaccine KidsHealth > For Teens > HPV Vaccine Print A A A What's in this article? ... 11 or 12 through age 21 If needed, kids can get the vaccine starting at age 9. continue How Does the ...

  17. A 2011 Risk/Benefit Analysis of the Anthrax Vaccine Immunization Program

    Science.gov (United States)

    2011-06-10

    immunization have included systemic lupus erythematosus , hypothyroidism, diabetes, cancers, Guillain-Barre´ syndrome, and multiple sclerosis.297...produces systematic reviews of the medical literature on specific topics.234 Cochrane reviews assemble primary literature, and provide evidence-based... Systematic Reviews 2009, Issue 2. Art. No: CD006403. DOI: 10.1002/14651858.CD006403.pub2, http://www2.cochrane.org/ reviews/en/ ab006403.html (accessed 20

  18. Current advances inhuman anthrax vaccine%炭疽疫苗新进展

    Institute of Scientific and Technical Information of China (English)

    宫嫚

    2002-01-01

    @@ 对于炭疽病的预防,我国既往使用的是"人用皮上划痕炭疽减毒活疫苗",接种后2d可产生免疫力,并可维持1年;应用A16R株炭疽芽孢菌气雾免疫也是安全有效的,吸入量为1亿个菌/人次,血清阳转率为80%以上.本文将炭疽疫苗的新进展综述如下:

  19. Pathogenic ecology: Where have all the pathogens gone? Anthrax: a classic case

    Science.gov (United States)

    Kiel, Johnathan; Walker, Wes W.; Andrews, Carrie J.; De Los Santos, Amy; Adams, Roy N.; Bucholz, Matthew W.; McBurnett, Shelly D.; Fuentes, Vladimir; Rizner, Karon E.; Blount, Keith W.

    2009-05-01

    Pathogenic ecology is the natural relationship to animate and inanimate components of the environment that support the sustainment of a pathogen in the environment or prohibit its sustainment, or their interactions with an introduced pathogen that allow for the establishment of disease in a new environment. The anthrax bacterium in the spore form has been recognized as a highly likely biological warfare or terrorist agent. The purpose of this work was to determine the environmental reservoir of Bacillus anthracis between outbreaks of anthrax and to examine the potential factors influencing the conversion of the Bacillus anthracis from a quiescent state to the disease causing state. Here we provide environmental and laboratory data for the cycling of Bacillus anthracis in plants to reconcile observations that contradict the soil borne hypothesis of anthrax maintenance in the environment.

  20. Naturally acquired anthrax antibodies in a cheetah (Acinonyx jubatus) in Botswana.

    Science.gov (United States)

    Good, Kyle M; Houser, Annmarie; Arntzen, Lorraine; Turnbull, Peter C B

    2008-07-01

    An outbreak of anthrax in the Jwana Game Reserve in Jwaneng, Botswana, was first observed when three cheetahs (Acinonyx jubatus) died of the disease in November 2004. In the aftermath of this event, banked serum samples collected from 23 wild-caught cheetahs were examined, by the inhibition enzyme-linked immunoassay (ELISA), for antibodies to the protective antigen (PA) of Bacillus anthracis. Of the 23 cheetahs, 16 regularly accessed the reserve. Antibodies to PA were detected in one cheetah collected in May 2004, indicating the disease was occurring well before it was first noticed. This appears to be the first demonstration of naturally acquired anthrax antibodies in cheetahs. The finding of one antibody-positive animal amongst at least 16 potentially exposed individuals is consistent with existing reports that it is uncommon for cheetahs to develop natural immunity to anthrax.

  1. The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock

    Directory of Open Access Journals (Sweden)

    Peter Q. Eichacker

    2011-09-01

    Full Text Available Outbreaks of Bacillus anthracis in the US and Europe over the past 10 years have emphasized the health threat this lethal bacteria poses even for developed parts of the world. In contrast to cutaneous anthrax, inhalational disease in the US during the 2001 outbreaks and the newly identified injectional drug use form of disease in the UK and Germany have been associated with relatively high mortality rates. One notable aspect of these cases has been the difficulty in supporting patients once shock has developed. Anthrax bacilli produce several different components which likely contribute to this shock. Growing evidence indicates that both major anthrax toxins may produce substantial cardiovascular dysfunction. Lethal toxin (LT can alter peripheral vascular function; it also has direct myocardial depressant effects. Edema toxin (ET may have even more pronounced peripheral vascular effects than LT, including the ability to interfere with the actions of conventional vasopressors. Additionally, ET also appears capable of interfering with renal sodium and water retention. Importantly, the two toxins exert their actions via quite different mechanisms and therefore have the potential to worsen shock and outcome in an additive fashion. Finally, both toxins have the ability to inhibit host defense and microbial clearance, possibly contributing to the very high bacterial loads noted in patients dying with anthrax. This last point is clinically relevant since emerging data has begun to implicate other bacterial components such as anthrax cell wall in the shock and organ injury observed with infection. Taken together, accumulating evidence regarding the potential contribution of LT and ET to anthrax-associated shock supports efforts to develop adjunctive therapies that target both toxins in patients with progressive shock.

  2. Certhrax toxin, an anthrax-related ADP-ribosyltransferase from Bacillus cereus.

    Science.gov (United States)

    Visschedyk, Danielle; Rochon, Amanda; Tempel, Wolfram; Dimov, Svetoslav; Park, Hee-Won; Merrill, A Rod

    2012-11-30

    We identified Certhrax, the first anthrax-like mART toxin from the pathogenic G9241 strain of Bacillus cereus. Certhrax shares 31% sequence identity with anthrax lethal factor from Bacillus anthracis; however, we have shown that the toxicity of Certhrax resides in the mART domain, whereas anthrax uses a metalloprotease mechanism. Like anthrax lethal factor, Certhrax was found to require protective antigen for host cell entry. This two-domain enzyme was shown to be 60-fold more toxic to mammalian cells than anthrax lethal factor. Certhrax localizes to distinct regions within mouse RAW264.7 cells by 10 min postinfection and is extranuclear in its cellular location. Substitution of catalytic residues shows that the mART function is responsible for the toxicity, and it binds NAD(+) with high affinity (K(D) = 52.3 ± 12.2 μM). We report the 2.2 Å Certhrax structure, highlighting its structural similarities and differences with anthrax lethal factor. We also determined the crystal structures of two good inhibitors (P6 (K(D) = 1.7 ± 0.2 μM, K(i) = 1.8 ± 0.4 μM) and PJ34 (K(D) = 5.8 ± 2.6 μM, K(i) = 9.6 ± 0.3 μM)) in complex with Certhrax. As with other toxins in this family, the phosphate-nicotinamide loop moves toward the NAD(+) binding site with bound inhibitor. These results indicate that Certhrax may be important in the pathogenesis of B. cereus.

  3. DNA vaccines

    Science.gov (United States)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  4. FLU VACCINATION

    CERN Multimedia

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  5. Periodontal vaccine

    Directory of Open Access Journals (Sweden)

    Ranjan Malhotra

    2011-01-01

    Full Text Available Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of increasing its power to resist or get rid of a disease. Vaccines are generally prophylactic, i.e. they ameliorate the effects of future infection. One such vaccine considered here is the "Periodontal vaccine". Till date, no preventive modality exists for periodontal disease and treatment rendered is palliative. Thus, availability of periodontal vaccine would not only prevent and modulate periodontal disease, but also enhance the quality of life of people for whom periodontal treatment cannot be easily obtained. The aim of the research should be development of a multispecies vaccine targeting the four prime periodontal pathogens, viz. Porphyromonas gingivalis, T. forsythus, T. denticola and A. comitans. Success is still elusive in case of periodontal vaccine due to the complex etiopathogenesis of the disease.

  6. [Henry Toussaint and Louis Pasteur. Rivalry over a vaccine].

    Science.gov (United States)

    Chevallier-Jussiau, Nadine

    2010-01-01

    Henry Toussaint (1847-1890) is a veterinary who studied in Veterinary School of Lyon with his great master Auguste Chauveau the famous physiologist. This place is the First School founded in Europe at the end of the XVIIIth century and has opened a way of thinking. His carrer brilliant and rich begins first in Lyon and then when he is named Professor of Anatomy and Physiology at the Veterinary School of Toulouse. Doctor of Science and Doctor of Medecine Toussaint applies "the experimental method" to his research in his laboratory and makes a lot of publications. He starts with Anatomy, then Physiology and soon he prioritizes his research to infestious diseases which cause serious damage to cattle in this time. He developes his own methods about anthrax an its "bacteridie", its nature, its way of culture and especially he studies the physiopathology of this disease. Pasteur is a renowned scientist who does study Microbiology at the same time in his laboratory in Paris, and precisely anthrax. He has explained his theories about "microbes" and has predominant advice. Toussaint admires Pasteur; in the year 1879 he finds first and isolates the microbe of "cholera des poules" (now Pasteurella) and gives Pasteur this new germ which will be used by Pasteur for his particular works about reducing of virulence by successive subcultures. In 1880 with his publishing on July 12 at the Academy of Science, Toussaint presents his successful result with an attenuated vaccine against anthrax: he has got protection against anthrax for dogs and sheep by using a vaccine which he has reduced off virulence by chemical manner. Academy congratulates him. Pasteur jealous of one's reputation contests the demonstration of Toussaint because he does not believe in the chemical method too different from his tests but will make use of this method for an experience open to the public in Pouilly-le-Fort in 1881. After this promotional event Pasteur will product and sell vaccines maked in his

  7. Redefining the Australian Anthrax Belt: Modeling the Ecological Niche and Predicting the Geographic Distribution of Bacillus anthracis.

    Directory of Open Access Journals (Sweden)

    Alassane S Barro

    2016-06-01

    Full Text Available The ecology and distribution of B. anthracis in Australia is not well understood, despite the continued occurrence of anthrax outbreaks in the eastern states of the country. Efforts to estimate the spatial extent of the risk of disease have been limited to a qualitative definition of an anthrax belt extending from southeast Queensland through the centre of New South Wales and into northern Victoria. This definition of the anthrax belt does not consider the role of environmental conditions in the distribution of B. anthracis. Here, we used the genetic algorithm for rule-set prediction model system (GARP, historical anthrax outbreaks and environmental data to model the ecological niche of B. anthracis and predict its potential geographic distribution in Australia. Our models reveal the niche of B. anthracis in Australia is characterized by a narrow range of ecological conditions concentrated in two disjunct corridors. The most dominant corridor, used to redefine a new anthrax belt, parallels the Eastern Highlands and runs from north Victoria to central east Queensland through the centre of New South Wales. This study has redefined the anthrax belt in eastern Australia and provides insights about the ecological factors that limit the distribution of B. anthracis at the continental scale for Australia. The geographic distributions identified can help inform anthrax surveillance strategies by public and veterinary health agencies.

  8. Combination therapy with antibiotics and anthrax immune globulin intravenous (AIGIV is potentially more effective than antibiotics alone in rabbit model of inhalational anthrax.

    Directory of Open Access Journals (Sweden)

    Srinivas Kammanadiminti

    Full Text Available BACKGROUND: We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by AIGIV over standard antibiotic treatment alone in a New Zealand white rabbit model of inhalational anthrax. METHODS: Rabbits were exposed to lethal dose of aerosolized spores of Bacillus anthracis (Ames strain and treated intravenously with either placebo, (normal immune globulin intravenous, IGIV or 15 U/kg of AIGIV, along with oral levofloxacin treatment at various time points (30-96 hours after anthrax exposure. RESULTS: The majority of treated animals (>88% survived in both treatment groups when treatment was initiated within 60 hours of post-exposure. However, reduced survival of 55%, 33% and 25% was observed for placebo + levofloxacin group when the treatment was initiated at 72, 84 and 96 hours post-exposure, respectively. Conversely, a survival rate of 65%, 40% and 71% was observed in the AIGIV + levofloxacin treated groups at these time points. CONCLUSIONS: The combination of AIGIV with antibiotics provided an improvement in survival compared to levofloxacin treatment alone when treatment was delayed up to 96 hours post-anthrax exposure. Additionally, AIGIV treatment when given as an adjunct therapy at any of the time points tested did not interfere with the efficacy of levofloxacin.

  9. Molecular Investigation of the Aum Shinrikyo Anthrax Release in Kameido, Japan

    OpenAIRE

    2001-01-01

    In 1993, the Aum Shinrikyo cult aerosolized Bacillus anthracis spores over Kameido, Japan. Spore samples were obtained from the release site, cultured, and characterized by molecular genetic typing. The isolates were consistent with strain Sterne 34F2, which is used in Japan for animal prophylaxis against anthrax.

  10. A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device

    NARCIS (Netherlands)

    Eker, Bilge; Yilmaz, Mahmut Deniz; Schlautmann, Stefan; Gardeniers, Johannes G.E.; Huskens, Jurriaan

    2011-01-01

    A supramolecular platform based on self-assembled monolayers (SAMs) has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detecti

  11. Antidotes to anthrax lethal factor intoxication. Part 2: structural modifications leading to improved in vivo efficacy.

    Science.gov (United States)

    Kim, Seongjin; Jiao, Guan-Sheng; Moayeri, Mahtab; Crown, Devorah; Cregar-Hernandez, Lynne; McKasson, Linda; Margosiak, Stephen A; Leppla, Stephen H; Johnson, Alan T

    2011-04-01

    New anthrax lethal factor inhibitors (LFIs) were designed based upon previously identified potent inhibitors 1a and 2. Combining the new core structures with modifications to the C2-side chain yielded analogs with improved efficacy in the rat lethal toxin model.

  12. Purification and biophysical characterization of the core protease domain of anthrax lethal factor.

    Science.gov (United States)

    Gkazonis, Petros V; Dalkas, Georgios A; Chasapis, Christos T; Vlamis-Gardikas, Alexios; Bentrop, Detlef; Spyroulias, Georgios A

    2010-06-04

    Anthrax lethal toxin (LeTx) stands for the major virulence factor of the anthrax disease. It comprises a 90kDa highly specific metalloprotease, the anthrax lethal factor (LF). LF possesses a catalytic Zn(2+) binding site and is highly specific against MAPK kinases, thus representing the most potent native biomolecule to alter and inactivate MKK [MAPK (mitogen-activated protein kinase) kinases] signalling pathways. Given the importance of the interaction between LF and substrate for the development of anti-anthrax agents as well as the potential treatment of nascent tumours, the analysis of the structure and dynamic properties of the LF catalytic site are essential to elucidate its enzymatic properties. Here we report the recombinant expression and purification of a C-terminal part of LF (LF(672-776)) that harbours the enzyme's core protease domain. The biophysical characterization and backbone assignments ((1)H, (13)C, (15)N) of the polypeptide revealed a stable, well folded structure even in the absence of Zn(2+), suitable for high resolution structural analysis by NMR.

  13. Protective Antigen (PA) and Toxin Neutralization (TNA) Antibody Patterns in Anthrax Vaccinees Undergoing Serial Plasmapheresis

    Science.gov (United States)

    2005-03-28

    Undergoing Serial Plasmapheresis Phillip R. Pittman,1 Susan F. Leitman,2 Julio G. Barrera Oro,3 Sarah L. Norris,4 Nina M. Marano,5 Manmohan V. Ranadive...plasmapheresis on serum proteins and immunoglobulins. Transfusion 15:467–472. 12. Gold, H. 1936 . Studies on anthrax. Clinical report of ten human cases

  14. Anthrax Toxins in Context of Bacillus anthracis Spores and Spore Germination.

    Science.gov (United States)

    Cote, Christopher K; Welkos, Susan L

    2015-08-17

    The interaction of anthrax toxin or toxin components with B. anthracis spores has been demonstrated. Germinating spores can produce significant amounts of toxin components very soon after the initiation of germination. In this review, we will summarize the work performed that has led to our understanding of toxin and spore interactions and discuss the complexities associated with these interactions.

  15. Erythropoiesis suppression is associated with anthrax lethal toxin-mediated pathogenic progression.

    Directory of Open Access Journals (Sweden)

    Hsin-Hou Chang

    Full Text Available Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality in animals and humans. Although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. Lethal toxin (LT is a major virulence factor of B. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (MAPKKs. Anthrax LT causes lethality and induces certain anthrax-like symptoms, such as anemia and hypoxia, in experimental mice. Mitogen-activated protein kinases (MAPKs are the downstream pathways of MAPKKs, and are important for erythropoiesis. This prompted us to hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic dysfunction. As revealed by colony-forming cell assays in this study, LT challenges significantly reduced mouse erythroid progenitor cells. In addition, in a proteolytic activity-dependent manner, LT suppressed cell survival and differentiation of cord blood CD34(+-derived erythroblasts in vitro. Suppression of cell numbers and the percentage of erythroblasts in the bone marrow were detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked through treatments of erythropoietin, significantly ameliorating the anemia and reducing the mortality of LT-treated mice. These data suggested that suppressed erythropoiesis is part of the pathophysiology of LT-mediated intoxication. Because specific treatments to overcome LT-mediated pathogenesis are still lacking, these efforts may help the development of effective treatments against anthrax.

  16. Protective Immunization Against Inhalational Anthrax: A Comparison of Minimally Invasive Delivery Platforms

    Science.gov (United States)

    2004-12-15

    associ- ated with the technique. Intranasal (inl) delivery is another alternative to im delivery. It has the potential to induce mucosal immunity [21–26...Leppla SH, Fujihashi K, McGhee JR. Effective mucosal immunity to anthrax: neutralizing antibodies and Th cell responses following nasal immunization

  17. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service

  18. FLU VACCINATION

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  19. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  20. Flu Vaccination

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service

  1. Louis Pasteur, from crystals of life to vaccination.

    Science.gov (United States)

    Berche, P

    2012-10-01

    Louis Pasteur (1822-1895) is an exceptional scientist who opened a new era in medicine and biology. Starting from studies on crystals of by-products of wine fermentation, he first defined a distinct chemistry between dead and living matters. He then showed the role of living microbes in the fermentation and putrefaction processes. This brought him to challenge the two-millennium-old theory of spontaneous generation, using remarkably well-designed experiments. His observations on epidemics in silkworms allowed him to demonstrate the role of specific germs in infectious diseases. His discovery of the vaccine against fowl cholera can be considered as the birth of immunology. Finally, he became universally recognized through his famous vaccinations against anthrax and rabies.

  2. Leptospirosis vaccines

    OpenAIRE

    Jin Li; Wang Zhijun; Węgrzyn Alicja

    2007-01-01

    Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the...

  3. Retrospective review of the case of cutaneous anthrax-malignant pustule from 1995 in 15-year old girl.

    Science.gov (United States)

    Kajfasz, Piotr; Bartoszcze, Michał; Borkowski, Piotr Karol; Basiak, Wojciech

    2014-01-01

    A 15-year-old girl was admitted to our Department with cutaneous lesion resembling black eschar. Anamnesis revealed that before getting ill she was wearing pullover made of rough sheep's wool and ornaments made of leather like straps. Cutaneous anthrax was confirmed by identification of B. anthracis in specimens from weeping ulceration, culture from black eschar, thermoprecipitation test, and bioassay on guinea pig. The girl was treated with crystalline Penicillin. She responded well to the therapy and recovered after 28 days. What attracts attention in presented case is the fact that the girl didn't belong to high risk group of human anthrax, which might lead to misdiagnosis. In 1990-1999, Poland there were reported 22 cases of anthrax - it was almost exclusively cutaneous form. In the years following 1999 antrax was reported even less often - in the period 1991-2013 it was recorded a total of 26 cutaneous anthrax cases.

  4. Detection of anthrax protective antigen (PA) using europium labeled anti-PA monoclonal antibody and time-resolved fluorescence.

    Science.gov (United States)

    Stoddard, Robyn A; Quinn, Conrad P; Schiffer, Jarad M; Boyer, Anne E; Goldstein, Jason; Bagarozzi, Dennis A; Soroka, Stephen D; Dauphin, Leslie A; Hoffmaster, Alex R

    2014-06-01

    Inhalation anthrax is a rare but acute infectious disease following adsorption of Bacillus anthracis spores through the lungs. The disease has a high fatality rate if untreated, but early and correct diagnosis has a significant impact on case patient recovery. The early symptoms of inhalation anthrax are, however, non-specific and current anthrax diagnostics are primarily dependent upon culture and confirmatory real-time PCR. Consequently, there may be a significant delay in diagnosis and targeted treatment. Rapid, culture-independent diagnostic tests are therefore needed, particularly in the context of a large scale emergency response. The aim of this study was to evaluate the ability of monoclonal antibodies to detect anthrax toxin proteins that are secreted early in the course of B. anthracis infection using a time-resolved fluorescence (TRF) immunoassay. We selected monoclonal antibodies that could detect protective antigen (PA), as PA83 and also PA63 and LF in the lethal toxin complex. The assay reliable detection limit (RDL) was 6.63×10(-6)μM (0.551ng/ml) for PA83 and 2.51×10(-5)μM (1.58ng/ml) for PA63. Despite variable precision and accuracy of the assay, PA was detected in 9 out of 10 sera samples from anthrax confirmed case patients with cutaneous (n=7), inhalation (n=2), and gastrointestinal (n=1) disease. Anthrax Immune Globulin (AIG), which has been used in treatment of clinical anthrax, interfered with detection of PA. This study demonstrates a culture-independent method of diagnosing anthrax through the use of monoclonal antibodies to detect PA and LF in the lethal toxin complex.

  5. The Evaluation of Post-Exposure Prophylaxis Models for Use in the Event of an Aerosolized Anthrax Attack

    Science.gov (United States)

    2014-09-01

    findings from the study of the accidental 1979 Sverdlovsk anthrax release in Russia , researchers have predicted that a 1- kg release of an anthrax...Equivalent Professional.” 167 Clare Stroud et al., “Commissioned Paper: A Cost and Speed Analysis of Strategies,” National Center for Biotechnology ...Bass. “Commissioned Paper: A Cost and Speed Analysis of Strategies.” National Center for Biotechnology Information, 2011. http

  6. Selecting Viruses for the Seasonal Influenza Vaccine

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  7. Seasonal Flu Vaccine Safety and Pregnant Women

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  8. Diagnostic performance characteristics of a rapid field test for anthrax in cattle.

    Science.gov (United States)

    Muller, Janine; Gwozdz, Jacek; Hodgeman, Rachel; Ainsworth, Catherine; Kluver, Patrick; Czarnecki, Jill; Warner, Simone; Fegan, Mark

    2015-07-01

    Although diagnosis of anthrax can be made in the field with a peripheral blood smear, and in the laboratory with bacterial culture or molecular based tests, these tests require either considerable experience or specialised equipment. Here we report on the evaluation of the diagnostic sensitivity and specificity of a simple and rapid in-field diagnostic test for anthrax, the anthrax immunochromatographic test (AICT). The AICT detects the protective antigen (PA) component of the anthrax toxin present within the blood of an animal that has died from anthrax. The test provides a result in 15min and offers the advantage of avoiding the necessity for on-site necropsy and subsequent occupational risks and environmental contamination. The specificity of the test was determined by testing samples taken from 622 animals, not infected with Bacillus anthracis. Diagnostic sensitivity was estimated on samples taken from 58 animals, naturally infected with B. anthracis collected over a 10-year period. All samples used to estimate the diagnostic sensitivity and specificity of the AICT were also tested using the gold standard of bacterial culture. The diagnostic specificity of the test was estimated to be 100% (99.4-100%; 95% CI) and the diagnostic sensitivity was estimated to be 93.1% (83.3-98.1%; 95% CI) (Clopper-Pearson method). Four samples produced false negative AICT results. These were among 9 samples, all of which tested positive for B. anthracis by culture, where there was a time delay between collection and testing of >48h and/or the samples were collected from animals that were >48h post-mortem. A statistically significant difference (P48h post-mortem 5 of 9 Se=56% (21-86.3%; 95% CI) (Clopper-Pearson method). Based upon these results a post hoc cut-off for use of the AICT of 48h post-mortem was applied, Se=100% (92.8-100%; 95% CI) and Sp=100% (99.4-100%; 95% CI). The high diagnostic sensitivity and specificity and the simplicity of the AICT enables it to be used for

  9. Frequent and seasonally variable sublethal anthrax infections are accompanied by short-lived immunity in an endemic system.

    Science.gov (United States)

    Cizauskas, Carrie A; Bellan, Steven E; Turner, Wendy C; Vance, Russell E; Getz, Wayne M

    2014-09-01

    Few studies have examined host-pathogen interactions in wildlife from an immunological perspective, particularly in the context of seasonal and longitudinal dynamics. In addition, though most ecological immunology studies employ serological antibody assays, endpoint titre determination is usually based on subjective criteria and needs to be made more objective. Despite the fact that anthrax is an ancient and emerging zoonotic infectious disease found world-wide, its natural ecology is not well understood. In particular, little is known about the adaptive immune responses of wild herbivore hosts against Bacillus anthracis. Working in the natural anthrax system of Etosha National Park, Namibia, we collected 154 serum samples from plains zebra (Equus quagga), 21 from springbok (Antidorcas marsupialis) and 45 from African elephants (Loxodonta africana) over 2-3 years, resampling individuals when possible for seasonal and longitudinal comparisons. We used enzyme-linked immunosorbent assays to measure anti-anthrax antibody titres and developed three increasingly conservative models to determine endpoint titres with more rigourous, objective mensuration. Between 52 and 87% of zebra, 0-15% of springbok and 3-52% of elephants had measurable anti-anthrax antibody titres, depending on the model used. While the ability of elephants and springbok to mount anti-anthrax adaptive immune responses is still equivocal, our results indicate that zebra in ENP often survive sublethal anthrax infections, encounter most B. anthracis in the wet season and can partially booster their immunity to B. anthracis. Thus, rather than being solely a lethal disease, anthrax often occurs as a sublethal infection in some susceptible hosts. Though we found that adaptive immunity to anthrax wanes rapidly, subsequent and frequent sublethal B. anthracis infections cause maturation of anti-anthrax immunity. By triggering host immune responses, these common sublethal infections may act as

  10. Modeling Tool for Decision Support during Early Days of an Anthrax Event

    Science.gov (United States)

    Meltzer, Martin I.; Shadomy, Sean; Bower, William A.; Hupert, Nathaniel

    2017-01-01

    Health officials lack field-implementable tools for forecasting the effects that a large-scale release of Bacillus anthracis spores would have on public health and hospitals. We created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examined the consequences of intervention choices. With only 3 days of case counts, the model can predict final attack sizes for simulated Sverdlovsk-like events (1979 USSR) with sufficient accuracy for decision making and confirms the value of early postexposure prophylaxis initiation. According to a baseline scenario, hospital treatment volume peaks 15 days after exposure, deaths peak earlier (day 5), and recovery peaks later (day 23). This tool gives public health, hospital, and emergency planners scenario-specific information for developing quantitative response plans for this threat. PMID:27983505

  11. Vaccine Safety

    Science.gov (United States)

    ... Tweet Share Compartir Back to School: Vaccines for Preteens Learn about the safety of Tdap, Meningococcal, and ... file Microsoft Word file Microsoft Excel file Audio/Video file Apple Quicktime file RealPlayer file Text file ...

  12. Typhoid Vaccine

    Science.gov (United States)

    ... serious disease. It is caused by bacteria called Salmonella Typhi. Typhoid causes a high fever, fatigue, weakness, stomach ... a typhoid carrier. • Laboratory workers who work with Salmonella Typhi bacteria. Inactivated typhoid vaccine (shot) • One dose provides ...

  13. Catastrophic Incident Recovery: Long-Term Recovery from an Anthrax Event Symposium

    Energy Technology Data Exchange (ETDEWEB)

    Lesperance, Ann M.

    2008-06-30

    On March 19, 2008, policy makers, emergency managers, and medical and Public Health officials convened in Seattle, Washington, for a workshop on Catastrophic Incident Recovery: Long-Term Recovery from an Anthrax Event. The day-long symposium was aimed at generating a dialogue about restoration and recovery through a discussion of the associated challenges that impact entire communities, including people, infrastructure, and critical systems.

  14. Anthrax toxins induce shock in rats by depressed cardiac ventricular function.

    Directory of Open Access Journals (Sweden)

    Linley E Watson

    Full Text Available Anthrax infections are frequently associated with severe and often irreversible hypotensive shock. The isolated toxic proteins of Bacillus anthracis produce a non-cytokine-mediated hypotension in rats by unknown mechanisms. These observations suggest the anthrax toxins have direct cardiovascular effects. Here, we characterize these effects. As a first step, we administered systemically anthrax lethal toxin (LeTx and edema toxin (EdTx to cohorts of three to twelve rats at different doses and determined the time of onset, degree of hypotension and mortality. We measured serum concentrations of the protective antigen (PA toxin component at various time points after infusion. Peak serum levels of PA were in the microg/mL range with half-lives of 10-20 minutes. With doses that produced hypotension with delayed lethality, we then gave bolus intravenous infusions of toxins to groups of four to six instrumented rats and continuously monitored blood pressure by telemetry. Finally, the same doses used in the telemetry experiments were given to additional groups of four rats, and echocardiography was performed pretreatment and one, two, three and twenty-four hours post-treatment. LeTx and EdTx each produced hypotension. We observed a doubling of the velocity of propagation and 20% increases in left ventricular diastolic and systolic areas in LeTx-treated rats, but not in EdTx-treated rats. EdTx-but not LeTx-treated rats showed a significant increase in heart rate. These results indicate that LeTx reduced left ventricular systolic function and EdTx reduced preload. Uptake of toxins occurs readily into tissues with biological effects occurring within minutes to hours of serum toxin concentrations in the microg/mL range. LeTx and EdTx yield an irreversible shock with subsequent death. These findings should provide a basis for the rational design of drug interventions to reduce the dismal prognosis of systemic anthrax infections.

  15. 炭疽病研究进展%Research advance in anthrax

    Institute of Scientific and Technical Information of China (English)

    王刚; 刘玉峰

    2003-01-01

    @@ 2001年发生在美国的恐怖袭击事件使炭疽病(Anthrax)再次受到广泛的关注,该事件使5名受害者死于吸入性炭疽,并在全世界范围内造成了一定程度的恐慌[1,2].

  16. Targeting the inflammasome and adenosine type-3 receptors improves outcome of antibiotic therapy in murine anthrax

    Institute of Scientific and Technical Information of China (English)

    Serguei; G; Popov; Taissia; G; Popova; Fatah; Kashanchi; Charles; Bailey

    2011-01-01

    AIM:To establish whether activation of adenosine type-3 receptors(A3Rs)and inhibition of interleukin- 1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores. METHODS:DBA/2 mice were challenged with Bacillus anthracis spores of the toxigenic Sterne strain 43F2. Survival of animals was monitored for 15 d.Ciprofloxacin treatment(50 mg/kg,once daily,intraperitoneally) was initiated at day+1 simultaneously with the ad- ministration of inhibitors,and continued for 10 d.Two doses(2.5 mg/kg and 12.5 mg/kg)of acetyl-tyrosylvalyl-alanyl-aspartyl-chloromethylketone(YVAD)and three doses(0.05,0.15 and 0.3 mg/kg)of 1-[2-Chloro- 6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1- deoxy-N-methyl-β-D-ribofuranuronamide(Cl-IB-MECA) were tested.Animals received YVAD on days 1-4,and Cl-IB-MECA on days 1-10 once daily,subcutaneously. Human lung epithelial cells in culture were challenged with spores or edema toxin and the effects of IB-MECAon phosphorylation of AKT and generation of cAMP were tested. RESULTS:We showed that the outcome of antibiotic treatment in a murine anthrax model could be substantially improved by co-administration of the caspase-1/4 inhibitor YVAD and the A3R agonist Cl-IB-MECA.Combination treatment with these substances and ciprofloxacin resulted in up to 90%synergistic protection.All untreated mice died,and antibiotic alone protected only 30% of animals.We conclude that both substances target the aberrant host signaling that underpins anthrax mortality. CONCLUSION:Our findings suggest new possibilities for combination therapy of anthrax with antibiotics,A3R agonists and caspase-1 inhibitors.

  17. Exoproteome analysis of a novel strain of Bacillus cereus implicated in disease resembling cutaneous anthrax.

    Science.gov (United States)

    Ghosh, Neha; Goel, Ajay Kumar; Alam, Syed Imteyaz

    2014-03-01

    Bacillus cereus belongs to B. cereus sensu lato group, shared by six other related species including Bacillus anthracis. B. anthracis is the causative agent for serious illness affecting a wide range of animals as well as humans and is a category A Biological and Toxin Warfare (BTW) agent. Recent studies indicate that a Bacillus species other than B. anthracis can cause anthrax-like disease and role of anthrax virulence plasmids (pXO1 and pXO2) on the pathogenicity of B. cereus has been documented. B. cereus strain TF5 was isolated from the tissue fluid of cutaneous anthrax-like skin lesions of a human patient from an anthrax endemic area in India. The strain harboured a PA gene, however, presence of pXO1 or pXO2-like plasmids could not be ascertained using reported primers. Abundant exoproteome of the strain in the early stationary phase was elucidated using a 2-DE MS approach and compared with that from a reference B. cereus strain. Analysis of proteins showing qualitative and quantitative differences between the two strains indicated an altered regulatory mechanism and putative role of S-layer protein and sphingomyelinase in the pathogenesis of strain TF5. Phylogenetic analysis of the S-layer protein indicated close affiliation of the strain with anthracis-like B. cereus strains such as B. cereus var. anthracis strain CI; whereas sphingomyelinase exhibited specific relationship with all the strains of B. anthracis apart from that with anthracis-like B. cereus strains.

  18. Blocking anthrax lethal toxin at the protective antigen channel by using structure-inspired drug design

    OpenAIRE

    Karginov, Vladimir A.; Nestorovich, Ekaterina M.; Moayeri, Mahtab; Leppla, Stephen H.; Bezrukov, Sergey M.

    2005-01-01

    Bacillus anthracis secretes three polypeptides: protective antigen (PA), lethal factor (LF), and edema factor (EF), which interact at the surface of mammalian cells to form toxic complexes. LF and EF are enzymes that target substrates within the cytosol; PA provides a heptameric pore to facilitate LF and EF transport into the cytosol. Other than administration of antibiotics shortly after exposure, there is currently no approved effective treatment for inhalational anthrax. Here we demonstrat...

  19. The Anthrax Terror. DOD’s Number-One Biological Threat

    Science.gov (United States)

    2000-01-01

    large quantities of anthrax and glanders organisms were grown. A Ger­ man agent, Capt Frederick Hinsch, used these to inoculate horses in Baltimore...program began receiv­ ing scrutiny under President F. W. de Klerk in the early 1990s, which led to the firing of nu­ merous scientists working the program...Rise of CB Weapons (New York: Humanities Press, 1971), 216; and Frederick R. Sidell, Ernest T. Takafuji, and David R. Franz, eds., Textbook of

  20. Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax

    Science.gov (United States)

    2008-06-21

    considered to be a treat- ment of choice for anthrax, numerous reports of -lactamase- producing strains and of treatment failures have appeared in the...model of Streptococcus pneumoniae infection (28), and in a rat model of S. aureus granuloma pouch infection (27). Mice ( female CD-1; body weight, 19...may have resulted from the expression of a cryptic or inducible -lactamase (37). DISCUSSION Oritavancin, a lipoglycopeptide antibiotic that is

  1. Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors

    Directory of Open Access Journals (Sweden)

    Chandhoke Vikas

    2006-02-01

    Full Text Available Abstract Background It has been recently reported that major pathogens Staphylococcus aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface syndecan-1 (Synd1 ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if acceleration of Synd1 shedding takes place in vitro upon treatment of epithelial cells with B. anthracis hemolysins, as well as in vivo during anthrax infection in mice. Results The isolated anthrax hemolytic proteins AnlB (sphingomyelinase and AnlO (cholesterol-binding pore-forming factor, as well as ClnA (B. cereus homolog of B. anthracis phosphatidyl choline-preferring phospholipase C cause accelerated shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial barrier integrity within a few hours. In comparison with hemolysins in a similar range of concentrations, anthrax lethal toxin (LT also accelerates shedding albeit at slower rate. Individual components of LT, lethal factor and protective antigen are inactive with regard to shedding. Inhibition experiments favor a hypothesis that activities of tested bacterial shedding inducers converge on the stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK signaling pathways, while JNK pathway seems to be irrelevant to accelerated shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged with Bacillus anthracis (Sterne spores. Elevated levels of shed ectodomain are readily detectable in circulation after 24 h. Conclusion The concerted acceleration of shedding by several virulence factors could represent a new pathogenic mechanism contributing to disruption of epithelial or endothelial integrity, hemorrhage, edema and abnormal cell signaling during anthrax infection.

  2. Highly predictive support vector machine (SVM) models for anthrax toxin lethal factor (LF) inhibitors.

    Science.gov (United States)

    Zhang, Xia; Amin, Elizabeth Ambrose

    2016-01-01

    Anthrax is a highly lethal, acute infectious disease caused by the rod-shaped, Gram-positive bacterium Bacillus anthracis. The anthrax toxin lethal factor (LF), a zinc metalloprotease secreted by the bacilli, plays a key role in anthrax pathogenesis and is chiefly responsible for anthrax-related toxemia and host death, partly via inactivation of mitogen-activated protein kinase kinase (MAPKK) enzymes and consequent disruption of key cellular signaling pathways. Antibiotics such as fluoroquinolones are capable of clearing the bacilli but have no effect on LF-mediated toxemia; LF itself therefore remains the preferred target for toxin inactivation. However, currently no LF inhibitor is available on the market as a therapeutic, partly due to the insufficiency of existing LF inhibitor scaffolds in terms of efficacy, selectivity, and toxicity. In the current work, we present novel support vector machine (SVM) models with high prediction accuracy that are designed to rapidly identify potential novel, structurally diverse LF inhibitor chemical matter from compound libraries. These SVM models were trained and validated using 508 compounds with published LF biological activity data and 847 inactive compounds deposited in the Pub Chem BioAssay database. One model, M1, demonstrated particularly favorable selectivity toward highly active compounds by correctly predicting 39 (95.12%) out of 41 nanomolar-level LF inhibitors, 46 (93.88%) out of 49 inactives, and 844 (99.65%) out of 847 Pub Chem inactives in external, unbiased test sets. These models are expected to facilitate the prediction of LF inhibitory activity for existing molecules, as well as identification of novel potential LF inhibitors from large datasets.

  3. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....

  4. Antipneumococcal vaccination

    Directory of Open Access Journals (Sweden)

    Gian Vincenzo Zuccotti

    2013-06-01

    Full Text Available Streptococcus pneumoniae (SP is a gram-positive bacterium with more than 90 known serotypes causing around 11% of all deaths worldwide in children aged 1-59 months. A new era in prevention of SP-related diseases started in at the beginning of 2000s when a 7-valent pneumococcal conjugate vaccine (PCV7 was recommended as the vaccine of choice in pediatric age. PCV7 dramatically reduced invasive pneumococcal diseases (IPD among children with indirect effects noted among other age groups as well. However, thanks to a strict surveillance network, an increase in non-vaccine serotypes (NVTs causing IPD was noted worldwide and in late 2000s a new second generation vaccine (13-valent pneumococcal conjugate vaccine-PCV13 with an expanded serotype coverage was licensed. Due to the lack of solid effectiveness data, up to know it is difficult to predict how the composition of NVTs will change after the large-scale introduction of PCV13 or whether the characteristics of the serotypes will change. Long-term surveillance of both IPD, pneumonia, acute otitis media and carriage will be crucial to ascertain whether these second generation vaccines are having the desired effect of reducing the incidence of diseases in the long term. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  5. Your child's first vaccines

    Science.gov (United States)

    ... multi.html . CDC review information for Multi Pediatric Vaccines: Your Child's First Vaccines: What you need to know (VIS): ... baby. 2. Some children should not get certain vaccines Most children can safely get all of these vaccines. But ...

  6. Ear Infection and Vaccines

    Science.gov (United States)

    ... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...

  7. Influenza Vaccine, Live Intranasal

    Science.gov (United States)

    ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT ... to your doctor or pharmacist about the best flu vaccine option for you or your family.

  8. Anthrax and the Geochemistry of Soils in the Contiguous United States

    Directory of Open Access Journals (Sweden)

    Dale W. Griffin

    2014-08-01

    Full Text Available Soil geochemical data from sample sites in counties that reported occurrences of anthrax in wildlife and livestock since 2000 were evaluated against counties within the same states (MN, MT, ND, NV, OR, SD and TX that did not report occurrences. These data identified the elements, calcium (Ca, manganese (Mn, phosphorus (P and strontium (Sr, as having statistically significant differences in concentrations between county type (anthrax occurrence versus no occurrence. Tentative threshold values of the lowest concentrations of each of these elements (Ca = 0.43 wt %, Mn = 142 mg/kg, P = 180 mg/kg and Sr = 51 mg/kg and average concentrations (Ca = 1.3 wt %, Mn = 463 mg/kg, P = 580 mg/kg and Sr = 170 mg/kg were identified from anthrax-positive counties as prospective investigative tools in determining whether an outbreak had “potential” or was “likely” at any given geographic location in the contiguous United States.

  9. Delayed toxicity associated with soluble anthrax toxin receptor decoy-Ig fusion protein treatment.

    Directory of Open Access Journals (Sweden)

    Diane Thomas

    Full Text Available Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream.

  10. The necrophagous fly anthrax transmission pathway: empirical and genetic evidence from wildlife epizootics.

    Science.gov (United States)

    Blackburn, Jason K; Van Ert, Matthew; Mullins, Jocelyn C; Hadfield, Ted L; Hugh-Jones, Martin E

    2014-08-01

    Early studies confirmed Bacillus anthracis in emesis and feces of flies under laboratory conditions, but there is little empirical field evidence supporting the roles of flies in anthrax transmission. We collected samples during outbreaks of anthrax affecting livestock and native and exotic wildlife on two ranches in West Texas (2009-2010). Sampling included animal carcasses, maggots, adult flies feeding on or within several meters of carcasses, and leaves from surrounding vegetation. Microbiology and PCR were used to detect B. anthracis in the samples. Viable B. anthracis and/or PCR-positive results were obtained from all represented sample types. Genetic analysis of B. anthracis samples using multilocus variable number tandem repeat analysis (MLVA) confirmed that each ranch represented a distinct genetic lineage. Within each ranch, we detected the same genotype of B. anthracis from carcasses, maggots, and adult flies. The results of this study provide evidence supporting a transmission cycle in which blowflies contaminate vegetation near carcasses that may then infect additional browsing animals during anthrax outbreaks in the shrubland environment of West Texas.

  11. A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection

    Directory of Open Access Journals (Sweden)

    Jane P. F. Bai

    2017-03-01

    Full Text Available Developing drugs to treat the toxic effects of lethal toxin (LT and edema toxin (ET produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound’s mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection.

  12. Confirmation of acute nitrate poisoning differentiating from anthrax in three Indian indigenous cattle

    Directory of Open Access Journals (Sweden)

    Kumaresan Nagarajan

    2015-03-01

    Full Text Available This article reports cases of nitrate poisoning in Indian indigenous cattle breeds comprising two Gir cows aging 4 years each, and one Barugur cow at 1.5 years of age. The cattle with case history of sudden death and oozing of partially clotted blood from the anal opening were brought to the Central University Laboratory (CUL, Center for Animal Health Studies (CAHS, Tamil Nadu Veterinary and Animal Sciences University (TANUVAS for diagnostic investigation with a suspicion of anthrax. According to anamnesis, all the animals were clinically normal and did not reveal any abnormality on the previous day. The animals were fed with recently harvested sorghum leaves and stalks. Smears examined for anthrax were found negative. Biological test (mice inoculation for anthrax was also negative. Gross lesions on necropsy examination of the carcases were suggestive of nitrate intoxication. Finally, nitrate intoxication of these cattle was confirmed by chemical and toxicological analysis of fodder, rumen content, aqueous humor, liver, kidney and urine.

  13. Efficacy and safety of AVP-21D9, an anthrax monoclonal antibody, in animal models and humans.

    Science.gov (United States)

    Malkevich, Nina V; Hopkins, Robert J; Bernton, Edward; Meister, Gabriel T; Vela, Eric M; Atiee, George; Johnson, Virginia; Nabors, Gary S; Aimes, Ronald T; Ionin, Boris; Skiadopoulos, Mario H

    2014-07-01

    Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. However, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. An anthrax antitoxin, AVP-21D9, also known as Thravixa (fully human anthrax monoclonal antibody), is being developed as a therapeutic agent against anthrax toxemia. The efficacy of AVP-21D9 in B. anthracis-infected New Zealand White rabbits and in cynomolgus macaques was evaluated, and its safety and pharmacokinetics were assessed in healthy human volunteers. The estimated mean elimination half-life values of AVP-21D9 in surviving anthrax-challenged rabbits and nonhuman primates (NHPs) ranged from approximately 2 to 4 days and 6 to 11 days, respectively. In healthy humans, the mean elimination half-life was in the range of 20 to 27 days. Dose proportionality was observed for the maximum serum concentration (Cmax) of AVP-21D9 and the area under the concentration-time curve (AUC). In therapeutic efficacy animal models, treatment with AVP-21D9 resulted in survival of up to 92% of the rabbits and up to 67% of the macaques. Single infusions of AVP-21D9 were well tolerated in healthy adult volunteers across all doses evaluated, and no serious adverse events were reported. (This study has been registered at ClinicalTrials.gov under registration no. NCT01202695.).

  14. Vaccination priorities.

    Science.gov (United States)

    Steffen, Robert; Baños, Ana; deBernardis, Chiara

    2003-02-01

    Selection of immunizations should be based on requirements and on risk of infection. According to the International Health Regulations, many countries require yellow fever vaccination and proof thereof as the International Certificate of vaccination. Additionally selected countries require proof of vaccination against cholera and meningococcal disease. A consultation for travel health advice is always an opportunity to ascertain that routine immunizations have been performed. Recommended immunizations often are more important for traveller's health than the required or routine ones. The most frequent vaccine preventable infection in non-immune travellers to developing countries is hepatitis A with an average incidence rate of 0.3% per month; in high risk backpackers or foreign-aid-volunteers this rate is 2.0%. Many immunizations are recommended for special risk groups only: there is a growing tendency in many countries to immunize all young travellers to developing countries against hepatitis B, as it is uncertain who will voluntarily or involuntarily get exposed. The attack rate of influenza in intercontinental travel is estimated to be 1%. Immunity against poliomyelitis remains essential for travel to Africa and parts of Asia. Many of the 0.2-0.4% who experience an animal bite are at risk of rabies. Typhoid fever is diagnosed with an incidence rate of 0.03% per month among travellers to the Indian subcontinent, North and West Africa (except Tunisia), and Peru, elsewhere this rate is 10-fold lower. Meningococcal disease, Japanese encephalitis, cholera and tuberculosis have been reported in travellers, but these infections are rare in this population. Although no travel health vaccine is cost beneficial, most professionals will offer protection against the frequent risks, while most would find it ridiculous to use all available vaccines in every traveller. It is essentially an arbitrary decision made on the risk level one wishes to recommend protection--but the

  15. Rotavirus Vaccine

    Science.gov (United States)

    ... including a severe allergy to latex. Babies with "severe combined immunodeficiency" (SCID) should not get rotavirus vaccine. Babies who have had a type of bowel blockage called "intussusception" should not get ... with moderate or severe diarrhea or vomiting. Check with your doctor if ...

  16. Polio Vaccine

    Science.gov (United States)

    ... Health Resources Share Polio Vaccine What is polio?Poliomyelitis (polio, for short) is a serious illness that can cause paralysis (when you can't move your arms and legs) or even death. Polio is caused by a virus. The virus can be spread by drinking water ...

  17. Comparative analysis of the immunologic response induced by the Sterne 34F2 live spore Bacillus anthracis vaccine in a ruminant model.

    Science.gov (United States)

    Ndumnego, Okechukwu C; Köhler, Susanne M; Crafford, Jannie; van Heerden, Henriette; Beyer, Wolfgang

    2016-10-01

    The Sterne 34F2 live spore vaccine (SLSV) developed in 1937 is the most widely used veterinary vaccine against anthrax. However, literature on the immunogenicity of this vaccine in a target ruminant host is scarce. In this study, we evaluated the humoral response to the Bacillus anthracis protective antigen (rPA), a recombinant bacillus collagen-like protein of anthracis (rBclA), formaldehyde inactivated spores (FIS) prepared from strain 34F2 and a vegetative antigen formulation prepared from a capsule and toxin deficient strain (CDC 1014) in Boer goats. The toxin neutralizing ability of induced antibodies was evaluated using an in vitro toxin neutralization assay. The protection afforded by the vaccine was also assessed in vaccinates. Anti-rPA, anti-FIS and lethal toxin neutralizing titres were superior after booster vaccinations, compared to single vaccinations. Qualitative analysis of humoral responses to rPA, rBclA and FIS antigens revealed a preponderance of anti-FIS IgG titres following either single or double vaccinations with the SLSV. Antibodies against FIS and rPA both increased by 350 and 300-fold following revaccinations respectively. There was no response to rBclA following vaccinations with the SLSV. Toxin neutralizing titres increased by 80-fold after single vaccination and 700-fold following a double vaccination. Lethal challenge studies in naïve goats indicated a minimum infective dose of 36 B. anthracis spores. Single and double vaccination with the SLSV protected 4/5 and 3/3 of goats challenged with>800 spores respectively. An early booster vaccination following the first immunization is suggested in order to achieve a robust immunity. Results from this study indicate that this crucial second vaccination can be administered as early as 3 months after the initial vaccination.

  18. Approval of raxibacumab for the treatment of inhalation anthrax under the US Food and Drug Administration Animal rule

    Directory of Open Access Journals (Sweden)

    Chia-Wei eTsai

    2015-12-01

    Full Text Available On December 14, 2012, the FDA approved raxibacumab, the first product developed under Project BioShield to achieve this milestone, and the first biologic product to be approved through the FDA animal efficacy rule (or Animal Rule. Raxibacumab is approved for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibiotic drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. The approval of Raxibacumab illustrates many of the challenges that product developers may encounter when pursuing approval under the Animal Rule and highlights a number of important regulatory and policy issues.

  19. Expression, Purification, and Biophysical Characterization of a Secreted Anthrax Decoy Fusion Protein in Nicotiana benthamiana

    Science.gov (United States)

    Karuppanan, Kalimuthu; Duhra-Gill, Sifti; Kailemia, Muchena J.; Phu, My L.; Lebrilla, Carlito B.; Dandekar, Abhaya M.; Rodriguez, Raymond L.; Nandi, Somen; McDonald, Karen A.

    2017-01-01

    Anthrax toxin receptor-mediated drug development for blocking anthrax toxin action has received much attention in recent decades. In this study, we produced a secreted anthrax decoy fusion protein comprised of a portion of the human capillary morphogenesis gene-2 (CMG2) protein fused via a linker to the fragment crystallizable (Fc) domain of human immunoglobulin G1 in Nicotiana benthamiana plants using a transient expression system. Using the Cauliflower Mosaic Virus (CaMV) 35S promoter and co-expression with the p19 gene silencing suppressor, we were able to achieve a high level of recombinant CMG2-Fc-Apo (rCMG2-Fc-Apo) protein accumulation. Production kinetics were observed up to eight days post-infiltration, and maximum production of 826 mg/kg fresh leaf weight was observed on day six. Protein A affinity chromatography purification of the rCMG2-Fc-Apo protein from whole leaf extract and apoplast wash fluid showed the homodimeric form under non-reducing gel electrophoresis and mass spectrometry analysis confirmed the molecular integrity of the secreted protein. The N-glycosylation pattern of purified rCMG2-Fc-Apo protein was analysed; the major portion of N-glycans consists of complex type structures in both protein samples. The most abundant (>50%) N-glycan structure was GlcNAc2(Xyl)Man3(Fuc)GlcNAc2 in rCMG2-Fc-Apo recovered from whole leaf extract and apoplast wash fluid. High mannose N-glycan structures were not detected in the apoplast wash fluid preparation, which confirmed the protein secretion. Altogether, these findings demonstrate that high-level production of rCMG2-Fc-Apo can be achieved by transient production in Nicotiana benthamiana plants with apoplast targeting. PMID:28054967

  20. Varicella (Chickenpox) Vaccine

    Science.gov (United States)

    ProQuad® (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine, Varicella Vaccine) ... up to about 1 person in 5) and measles-like rash (about 1 person in 20) than MMR and varicella vaccines given separately. Moderate Problems:Seizure (jerking or staring) ...

  1. Biochip for the Detection of Bacillus anthracis Lethal Factor and Therapeutic Agents against Anthrax Toxins

    Science.gov (United States)

    Silin, Vitalii; Kasianowicz, John J.; Michelman-Ribeiro, Ariel; Panchal, Rekha G.; Bavari, Sina; Robertson, Joseph W. F.

    2016-01-01

    Tethered lipid bilayer membranes (tBLMs) have been used in many applications, including biosensing and membrane protein structure studies. This report describes a biosensor for anthrax toxins that was fabricated through the self-assembly of a tBLM with B. anthracis protective antigen ion channels that are both the recognition element and electrochemical transducer. We characterize the sensor and its properties with electrochemical impedance spectroscopy and surface plasmon resonance. The sensor shows a sensitivity similar to ELISA and can also be used to rapidly screen for molecules that bind to the toxins and potentially inhibit their lethal effects. PMID:27348008

  2. Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor

    Energy Technology Data Exchange (ETDEWEB)

    Maize, Kimberly M.; Kurbanov, Elbek K.; Johnson, Rodney L.; Amin, Elizabeth Ambrose; Finzel, Barry C. (UMM)

    2016-07-05

    The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1'* which might afford new opportunities to design selective inhibitors that target this subsite.

  3. Detecting anthrax in the palm of your hand: applications of a smartphone microscope

    Energy Technology Data Exchange (ETDEWEB)

    Erikson, Rebecca L.; Hutchison, Janine R.

    2015-11-14

    Bacillus anthracis is a bacterial pathogen that causes the disease anthrax. In 2001, B. anthracis was used in a bioterrorism attack in the United States that resulted in 22 individuals becoming infected, 5 of whom died as a result of this attack. A great deal of attention has been dedicated to responding to bioterrorism events to reduce the potential loss of lives. One such area of research has focused on the development of new technologies to detect and respond to the intentional release of bacterial pathogens such as B. anthracis.

  4. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... to 2-Year-Old Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: Meningococcal Vaccines ... or her parents, and the doctor. Why the Vaccines Are Recommended Meningococcal disease is caused by a ...

  5. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... to 2-Year-Old Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: Meningococcal Vaccines Print ... of Shots? Meningitis How Do I Know Which Vaccines My Kids Need? How Can I Comfort My Baby During ...

  6. Your Baby's First Vaccines

    Science.gov (United States)

    ... of Page Some children should not get certain vaccines Most children can safely get all of these vaccines. But ... has ever had a severe reaction after any vaccination. A child who has a severe (life-threatening) allergy to ...

  7. Vaccines.gov

    Science.gov (United States)

    ... supported by science, on vaccine safety. Are your child’s vaccines up to date? Getting all recommended vaccines on time can protect your child from serious diseases. Protect your community! Did you ...

  8. Vaccines Stop Illness

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  9. Vaccines and Thimerosal

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Thimerosal in Vaccines Recommend on Facebook Tweet Share Compartir Thimerosal is ... harm. Thimerosal prevents the growth of bacteria in vaccines. Thimerosal is added to vials of vaccine that ...

  10. Vaccination in Fish

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar

    vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...... respond to vaccination by increasing the specific antibody titer and by activating the cellular responses. My talk will cover vaccination methods in fish, immune responses and some adverse effect of oil-adjuvanted vaccines in fish with reference to our work in rainbow trout, Oncorhynchus mykiss....

  11. Production of vaccines for treatment of infectious diseases by transgenic plants

    Directory of Open Access Journals (Sweden)

    Kristina LEDL

    2016-04-01

    Full Text Available Since the first pathogen antigen was expressed in transgenic plants with the aim of producing edible vaccine in early 1990s, transgenic plants have become a well-established expression system for production of alternative vaccines against various human and animal infectious diseases. The main focus of plant expression systems in the last five years has been on improving expression of well-studied antigens such as porcine reproductive and respiratory syndrome (PRRSV, bovine viral diarrhea disease virus (BVDV, footh and mouth disease virus (FMDV, hepatitis B surface antigen (HBsAg, rabies G protein, rotavirus, Newcastle disease virus (NDV, Norwalk virus capsid protein (NVCP, avian influenza virus H5N1, Escherichia coli heat-labile enterotoxin subunit B (LT-B, cholera toxin B (CT-B, human immunodeficiency virus (HIV, artherosclerosis, ebola and anthrax. Significant increases in expression have been obtained using improved expression vectors, different plant species and transformation methods.

  12. Isolation, Specification, Molecular Biology Assessment and Vaccine Development of Clostridium in Iran: A Review

    Directory of Open Access Journals (Sweden)

    Pilehchian Langroudi

    2015-11-01

    Full Text Available Context The genus Clostridium, which consists of spore-forming anaerobes, can cause different diseases in domestic animals and human and some of them are serious and fatal. According to the increasing economic value of the meat and milk-producing animals, the importance of a certain number of such diseases in Iran is unquestionable. Evidence Acquisition In Iran, and probably in other Near East countries, much attention was formerly paid to control more serious contagious diseases, such as rinderpest, anthrax, etc. resulting in the negligence of diseases such as enterotoxaemia. The epizootiological position has now changed whereby some of the contagious diseases are eradicated or are being methodically controlled. Conclusions This review refers to the veterinary aspects of the anaerobic clostridial diseases and vaccine development concerning the works carried out in Iran and especially at the Razi Serum and Vaccine Research Institute in the last eight decades.

  13. Vaccine-Preventable Disease Photos

    Science.gov (United States)

    Home | About | A-Z | Contact | Follow Vaccine Information You Need VACCINE BASICS Evaluating Online Health Information FAQs How Vaccines Work Importance of Vaccines Paying for Vaccines State Immunization Programs ...

  14. [Vaccination against mouse pox].

    Science.gov (United States)

    Mahnel, H

    1985-01-01

    Attenuated MVA-strain of vaccinia virus has been efficient in the control of enzootic mousepox and in prophylactic vaccination. The virus has been used as a live vaccine for prophylactic and emergency vaccinations as well as for sanitation of populations. More than 100 000 vaccinations were carried out safely. Even after suspension of the obligatory vaccination of humans against smallpox the MVA-vaccine can be employed without risk and danger.

  15. Hepatitis B Vaccine

    Science.gov (United States)

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  16. Statistical pattern matching facilitates the design of polyvalent inhibitors of anthrax and cholera toxins.

    Science.gov (United States)

    Rai, Prakash; Padala, Chakradhar; Poon, Vincent; Saraph, Arundhati; Basha, Saleem; Kate, Sandesh; Tao, Kevin; Mogridge, Jeremy; Kane, Ravi S

    2006-05-01

    Numerous biological processes involve the recognition of a specific pattern of binding sites on a target protein or surface. Although ligands displayed by disordered scaffolds form stochastic rather than specific patterns, theoretical models predict that recognition will occur between patterns that are characterized by similar or "matched" statistics. Endowing synthetic biomimetic structures with statistical pattern matching capabilities may improve the specificity of sensors and resolution of separation processes. We demonstrate that statistical pattern matching enhances the potency of polyvalent therapeutics. We functionalized liposomes with an inhibitory peptide at different densities and observed a transition in potency at an interpeptide separation that matches the distance between ligand-binding sites on the heptameric component of anthrax toxin. Pattern-matched polyvalent liposomes inhibited anthrax toxin in vitro at concentrations four orders of magnitude lower than the corresponding monovalent peptide, and neutralized this toxin in vivo. Statistical pattern matching also enhanced the potency of polyvalent inhibitors of cholera toxin. This facile strategy should be broadly applicable to the detection and neutralization of toxins and pathogens.

  17. A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Jurriaan Huskens

    2011-10-01

    Full Text Available A supramolecular platform based on self-assembled monolayers (SAMs has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detection. A Eu(III-EDTA complex was bound to β-cyclodextrin monolayers via orthogonal supramolecular host-guest interactions. The self-assembly of the Eu(III-EDTA conjugate and naphthalene β-diketone as an antenna resulted in the formation of a highly luminescent lanthanide complex on the microchannel surface. Detection of different phosphate anions and aromatic carboxylic acids was demonstrated by monitoring the decrease in red emission following displacement of the antenna by the analyte. Among these analytes, adenosine triphosphate (ATP and pyrophosphate, as well as dipicolinic acid (DPA which is a biomarker for anthrax, showed a strong response. Parallel fabrication of five sensing SAMs in a single multichannel chip was performed, as a first demonstration of phosphate and carboxylic acid screening in a multiplexed format that allows a general detection platform for both analyte systems in a single test run with µM and nM detection sensitivity for ATP and DPA, respectively.

  18. Rapid homogenous time-resolved fluorescence (HTRF) immunoassay for anthrax detection.

    Science.gov (United States)

    Cohen, Noam; Mechaly, Adva; Mazor, Ohad; Fisher, Morly; Zahavy, Eran

    2014-05-01

    Infection with Bacillus anthracsis spores induces an acute anthrax disease that can cause casualties and death in untreated cases. Thus rapid diagnosis of anthrax at early stage of the disease is essential to allow an effective treatment. Here we present the development of rapid and sensitive homogenous time-resolved fluorescence (HTRF) immunoassays based on the energy transfer process of europium cryptate (EuK) donor to AlexaFluor647 acceptor. The energy transfer process is limited to d bacteremia in infected hosts, using two monoclonal anti-PA antibodies that specifically recognize two different epitopes on the PA molecule. The assay was sensitive enabling detection of 2 ng/ml PA in the serum of B. anthracsis-infected rabbits in only 15 min assay. Additionally, HTRF assay was developed for the detection of bacterial spores using polyclonal anti-spore antibodies that recognize many epitopes on the bacterial surface. The assay enabled the detection of 2 × 10(6) spores/ml in 30 min assay and was specific, showing no cross reactivity with closely related non-virulent bacillus cereus strain. This study describes the use of the HTRF assay for the detection of both singled-epitope (proteins) and multi-epitope (particles) as rapid, simple and sensitive method that can be used at the time that fast results are needed to allow an effective medical care.

  19. Anthrax lethal toxin suppresses high glucose induced VEGF over secretion through a post-translational mechanism

    Institute of Scientific and Technical Information of China (English)

    Wei-Wei; Zhang; Xin; Wang; Ping; Xie; Song-Tao; Yuan; Qing-Huai; Liu

    2015-01-01

    AIM: To prove anthrax lethal toxin(Le Tx) blocks the mitogen activated protein kinases(MAPKs) activation by degrading the MAPK/ERK kinases(MEKs) to suppress vascular endothelial growth factor(VEGF) secretion.METHODS: Human adult retinal pigmented epithelium(ARPE) cells were cultured and treated with normal glucose, high glucose or high glucose with Le Tx for additional 24, 48 or 72 h for viable cell count. Total RNA from the ARPE was isolated for reverse transcription polymerase chain reaction(RT-PCR). The conditioned medium of ARPE cells treated in different group for 48 h was filtered and diluted to detect the concentration of VEGF by enzyme-linked immunosorbant assays.Evaluate the role of MEK/MAPK pathway in the secretion of VEGF by immunoblotting. RESULTS: In this study, we proved high glucose induced activation of the MAPK extracellular signal-regulated kinase(ERK1/2) and p38 in the ARPE cell line was blocked by anthrax Le Tx. Le Tx also inhibited high glucose induced ARPE cell over proliferation.CONCLUSION: Le Tx suppressed high glucose induced VEGF over secretion in the ARPE cells, mainly through a post-translational mechanism.

  20. Detection of anthrax lef with DNA-based photonic crystal sensors

    Science.gov (United States)

    Zhang, Bailin; Dallo, Shatha; Peterson, Ralph; Hussain, Syed; Weitao, Tao; Ye, Jing Yong

    2011-12-01

    Bacillus anthracis has posed a threat of becoming biological weapons of mass destruction due to its virulence factors encoded by the plasmid-borne genes, such as lef for lethal factor. We report the development of a fast and sensitive anthrax DNA biosensor based on a photonic crystal structure used in a total-internal-reflection configuration. For the detection of the lef gene, a single-stranded DNA lef probe was biotinylated and immobilized onto the sensor via biotin-streptavidin interactions. A positive control, lef-com, was the complementary strand of the probe, while a negative control was an unrelated single-stranded DNA fragment from the 16S rRNA gene of Acinetobacter baumannii. After addition of the biotinylated lef probe onto the sensor, significant changes in the resonance wavelength of the sensor were observed, resulting from binding of the probe to streptavidin on the sensor. The addition of lef-com led to another significant increase as a result of hybridization between the two DNA strands. The detection sensitivity for the target DNA reached as low as 0.1 nM. In contrast, adding the unrelated DNAs did not cause an obvious shift in the resonant wavelength. These results demonstrate that detection of the anthrax lef by the photonic crystal structure in a total-internal-reflection sensor is highly specific and sensitive.

  1. Functions of phenylalanine residues within the beta-barrel stem of the anthrax toxin pore.

    Directory of Open Access Journals (Sweden)

    Jie Wang

    Full Text Available BACKGROUND: A key step of anthrax toxin action involves the formation of a protein-translocating pore within the endosomal membrane by the Protective Antigen (PA moiety. Formation of this transmembrane pore by PA involves interaction of the seven 2beta2-2beta3 loops of the heptameric precursor to generate a 14-strand transmembrane beta barrel. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects on pore formation, protein translocation, and cytotoxicity, of mutating two phenylalanines, F313 and F314, that lie at the tip the beta barrel, and a third one, F324, that lies part way up the barrel. CONCLUSIONS/SIGNIFICANCE: Our results show that the function of these phenylalanine residues is to mediate membrane insertion and formation of stable transmembrane channels. Unlike F427, a key luminal residue in the cap of the pore, F313, F314, and F324 do not directly affect protein translocation through the pore. Our findings add to our knowledge of structure-function relationships of a key virulence factor of the anthrax bacillus.

  2. The Mountain Meadows Massacre and "poisoned springs": scientific testing of the more recent, anthrax theory.

    Science.gov (United States)

    Perego, Ugo A; Achilli, Alessandro; Ekins, Jayne E; Milani, Lucio; Lari, Martina; Pilli, Elena; Brown, Alexis; Price, Erin P; Wolken, Spenser R; Matthews, Molly; Allen, Christina A; Pearson, Talima R; Angerhofer, Norman; Caramelli, David; Kupferschmid, Tim; Keim, Paul S; Woodward, Scott R

    2013-01-01

    It has been recorded that one of the possible causes that eventually escalated into the 1857 manslaughter at Mountain Meadows in Southern Utah was the poisoning of an open spring by the Fancher-Baker party as they crossed the Utah territory on their way from Arkansas to California. Historical accounts report that a number of cattle died, followed by human casualties from those that came in contact with the dead animals. Even after the Arkansas party departed, animals continued to perish and people were still afflicted by some unknown plague. Proctor Hancock Robison, a local 14-year-old boy, died shortly after skinning one of the "poisoned" cows. A careful review of the historical records, along with the more recent scientific literature, seems to exclude the likelihood of actual poisoning in favor of a more recent theory that would point to the bacterium Bacillus anthracis as the possible cause of human and animal deaths. In order to test this hypothesis, Proctor's remains were exhumed, identified through mitochondrial DNA analysis, and tested for the presence of anthrax spores. Although preliminary testing of remains and soil was negative, description of the clinical conditions that affected Proctor and other individuals does not completely rule out the hypothesis of death by anthrax.

  3. Detection of anthrax lef with DNA-based photonic crystal sensors.

    Science.gov (United States)

    Zhang, Bailin; Dallo, Shatha; Peterson, Ralph; Hussain, Syed; Weitao, Tao; Ye, Jing Yong

    2011-12-01

    Bacillus anthracis has posed a threat of becoming biological weapons of mass destruction due to its virulence factors encoded by the plasmid-borne genes, such as lef for lethal factor. We report the development of a fast and sensitive anthrax DNA biosensor based on a photonic crystal structure used in a total-internal-reflection configuration. For the detection of the lef gene, a single-stranded DNA lef probe was biotinylated and immobilized onto the sensor via biotin-streptavidin interactions. A positive control, lef-com, was the complementary strand of the probe, while a negative control was an unrelated single-stranded DNA fragment from the 16S rRNA gene of Acinetobacter baumannii. After addition of the biotinylated lef probe onto the sensor, significant changes in the resonance wavelength of the sensor were observed, resulting from binding of the probe to streptavidin on the sensor. The addition of lef-com led to another significant increase as a result of hybridization between the two DNA strands. The detection sensitivity for the target DNA reached as low as 0.1 nM. In contrast, adding the unrelated DNAs did not cause an obvious shift in the resonant wavelength. These results demonstrate that detection of the anthrax lef by the photonic crystal structure in a total-internal-reflection sensor is highly specific and sensitive.

  4. Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.

    Directory of Open Access Journals (Sweden)

    Heather M Scobie

    Full Text Available The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA toxin subunit from forming pores until exposure to low pH. PA forms pores at pH approximately 6.0 or below when it is bound to ANTXR1, but only at pH approximately 5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation.

  5. Examining the CDCynergy Event Assessment Tool: an investigation of the anthrax crisis in Boca Raton, Florida.

    Science.gov (United States)

    McIntyre, J J; Venette, Steven

    2006-09-01

    This paper examines the dependability of the Event Assessment Tool over time. The latter is part of a CD-ROM--Emergency Risk Communication CDCynergy--distributed primarily to public information officers in the United States by the Centers for Disease Control and Prevention. The Event Assessment Tool is designed to aid emergency professionals in identifying the magnitude of a crisis event and to suggest appropriate actions to confront such a situation. Applied twice during the 2001 anthrax bioterrorism crisis in Boca Raton, Florida, the tool functioned in a binary manner by first indicating a moderate crisis level (on 4 October) and then four days later (on 8 October) a highly intense crisis, suggesting that it is time sensitive. This anthrax event provides an opportunity for crisis and disaster managers to understand the dynamic nature of crises. Rapid changes during these types of events suggest that any metric used to predict intensity must account for this variability. Additional limitations and implications of the tool are discussed.

  6. Lethal factor, but not edema factor, is required to cause fatal anthrax in cynomolgus macaques after pulmonary spore challenge.

    Science.gov (United States)

    Hutt, Julie A; Lovchik, Julie A; Drysdale, Melissa; Sherwood, Robert L; Brasel, Trevor; Lipscomb, Mary F; Lyons, C Rick

    2014-12-01

    Inhalational anthrax is caused by inhalation of Bacillus anthracis spores. The ability of B. anthracis to cause anthrax is attributed to the plasmid-encoded A/B-type toxins, edema toxin (edema factor and protective antigen) and lethal toxin (lethal factor and protective antigen), and a poly-d-glutamic acid capsule. To better understand the contribution of these toxins to the disease pathophysiology in vivo, we used B. anthracis Ames strain and isogenic toxin deletion mutants derived from the Ames strain to examine the role of lethal toxin and edema toxin after pulmonary spore challenge of cynomolgus macaques. Lethal toxin, but not edema toxin, was required to induce sustained bacteremia and death after pulmonary challenge with spores delivered via bronchoscopy. After intravenous challenge with bacilli to model the systemic phase of infection, lethal toxin contributed to bacterial proliferation and subsequent host death to a greater extent than edema toxin. Deletion of protective antigen resulted in greater loss of virulence after intravenous challenge with bacilli than deletion of lethal toxin or edema toxin alone. These findings are consistent with the ability of anti-protective antigen antibodies to prevent anthrax and suggest that lethal factor is the dominant toxin that contributes to the escape of significant numbers of bacilli from the thoracic cavity to cause anthrax after inhalation challenge with spores.

  7. Specific, sensitive, and quantitative enzyme-linked immunosorbent assay for human immunoglobulin G antibodies to anthrax toxin protective antigen.

    Science.gov (United States)

    Quinn, Conrad P; Semenova, Vera A; Elie, Cheryl M; Romero-Steiner, Sandra; Greene, Carolyn; Li, Han; Stamey, Karen; Steward-Clark, Evelene; Schmidt, Daniel S; Mothershed, Elizabeth; Pruckler, Janet; Schwartz, Stephanie; Benson, Robert F; Helsel, Leta O; Holder, Patricia F; Johnson, Scott E; Kellum, Molly; Messmer, Trudy; Thacker, W Lanier; Besser, Lilah; Plikaytis, Brian D; Taylor, Thomas H; Freeman, Alison E; Wallace, Kelly J; Dull, Peter; Sejvar, Jim; Bruce, Erica; Moreno, Rosa; Schuchat, Anne; Lingappa, Jairam R; Martin, Sandra K; Walls, John; Bronsdon, Melinda; Carlone, George M; Bajani-Ari, Mary; Ashford, David A; Stephens, David S; Perkins, Bradley A

    2002-10-01

    The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted the need for a sensitive, reproducible, and specific laboratory test for the confirmatory diagnosis of human anthrax. The Centers for Disease Control and Prevention developed, optimized, and rapidly qualified an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum. The qualified ELISA had a minimum detection limit of 0.06 micro g/mL, a reliable lower limit of detection of 0.09 micro g/mL, and a lower limit of quantification in undiluted serum specimens of 3.0 micro g/mL anti-PA IgG. The diagnostic sensitivity of the assay was 97.8%, and the diagnostic specificity was 97.6%. A competitive inhibition anti-PA IgG ELISA was also developed to enhance diagnostic specificity to 100%. The anti-PA ELISAs proved valuable for the confirmation of cases of cutaneous and inhalational anthrax and evaluation of patients in whom the diagnosis of anthrax was being considered.

  8. Role of visible light-activated photocatalyst on the reduction of anthrax spore-induced mortality in mice.

    Directory of Open Access Journals (Sweden)

    Jyh-Hwa Kau

    Full Text Available BACKGROUND: Photocatalysis of titanium dioxide (TiO(2 substrates is primarily induced by ultraviolet light irradiation. Anion-doped TiO(2 substrates were shown to exhibit photocatalytic activities under visible-light illumination, relative environmentally-friendly materials. Their anti-spore activity against Bacillus anthracis, however, remains to be investigated. We evaluated these visible-light activated photocatalysts on the reduction of anthrax spore-induced pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Standard plating method was used to determine the inactivation of anthrax spore by visible light-induced photocatalysis. Mouse models were further employed to investigate the suppressive effects of the photocatalysis on anthrax toxin- and spore-mediated mortality. We found that anti-spore activities of visible light illuminated nitrogen- or carbon-doped titania thin films significantly reduced viability of anthrax spores. Even though the spore-killing efficiency is only approximately 25%, our data indicate that spores from photocatalyzed groups but not untreated groups have a less survival rate after macrophage clearance. In addition, the photocatalysis could directly inactivate lethal toxin, the major virulence factor of B. anthracis. In agreement with these results, we found that the photocatalyzed spores have tenfold less potency to induce mortality in mice. These data suggest that the photocatalysis might injury the spores through inactivating spore components. CONCLUSION/SIGNIFICANCE: Photocatalysis induced injuries of the spores might be more important than direct killing of spores to reduce pathogenicity in the host.

  9. Patients' request for and emergency physicians' prescription of antimicrobial prophylaxis for anthrax during the 2001 bioterrorism-related outbreak

    Directory of Open Access Journals (Sweden)

    Aber Robert C

    2005-01-01

    Full Text Available Abstract Background Inappropriate use of antibiotics by individuals worried about biological agent exposures during bioterrorism events is an important public health concern. However, little is documented about the extent to which individuals with self-identified risk of anthrax exposure approached physicians for antimicrobial prophylaxis during the 2001 bioterrorism attacks in the United States. Methods We conducted a telephone survey of randomly selected members of the Pennsylvania Chapter of the American College of Emergency Physicians to assess patients' request for and emergency physicians' prescription of antimicrobial agents during the 2001 anthrax attacks. Results Ninety-seven physicians completed the survey. Sixty-four (66% respondents had received requests from patients for anthrax prophylaxis; 16 (25% of these physicians prescribed antibiotics to a total of 23 patients. Ten physicians prescribed ciprofloxacin while 8 physicians prescribed doxycycline. Conclusion During the 2001 bioterrorist attacks, the majority of the emergency physicians we surveyed encountered patients who requested anthrax prophylaxis. Public fears may lead to a high demand for antibiotic prophylaxis during bioterrorism events. Elucidation of the relationship between public health response to outbreaks and outcomes would yield insights to ease burden on frontline clinicians and guide strategies to control inappropriate antibiotic allocation during bioterrorist events.

  10. Anthrax lethal toxin-mediated killing of human and murine dendritic cells impairs the adaptive immune response.

    Directory of Open Access Journals (Sweden)

    Abdelkrim Alileche

    2005-10-01

    Full Text Available Many pathogens have acquired strategies to combat the immune response. Bacillus anthracis interferes with host defenses by releasing anthrax lethal toxin (LT, which inactivates mitogen-activated protein kinase pathways, rendering dendritic cells (DCs and T lymphocytes nonresponsive to immune stimulation. However, these cell types are considered resistant to killing by LT. Here we show that LT kills primary human DCs in vitro, and murine DCs in vitro and in vivo. Kinetics of LT-mediated killing of murine DCs, as well as cell death pathways induced, were dependent upon genetic background: LT triggered rapid necrosis in BALB/c-derived DCs, and slow apoptosis in C57BL/6-derived DCs. This is consistent with rapid and slow killing of LT-injected BALB/c and C57BL/6 mice, respectively. We present evidence that anthrax LT impairs adaptive immunity by specifically targeting DCs. This may represent an immune-evasion strategy of the bacterium, and contribute to anthrax disease progression. We also established that genetic background determines whether apoptosis or necrosis is induced by LT. Finally, killing of C57BL/6-derived DCs by LT mirrors that of human DCs, suggesting that C57BL/6 DCs represent a better model system for human anthrax than the prototypical BALB/c macrophages.

  11. Maintaining U.S. Government Business Operations within the National Capital Region after an Aerosolized Anthrax Attack

    Science.gov (United States)

    2008-04-28

    Association, Volume 287, Number 17, 2237. 18 John G. Bartlett, Thomas V. Ingelsby, Jr., and Luciana Borio, “Management of Anthrax,” October 1, 2002...Human Services and the Secretary of Homeland Security, September 20, 2007. 46 Inglesby, 2244. 47 Luciana L. Borio, M.D., “CBN Report: Immunological

  12. Vaccines and vaccinations. The strategic issues.

    Science.gov (United States)

    Ford, R B

    2001-05-01

    The rapid proliferation of companion animal vaccines, advances in diagnostic and vaccine technology, and concerns over vaccine safety are clearly among the most important issues practicing veterinarians face as we enter the 21st century. Although many would argue that these are already issues, the future promises to be especially challenging as the vaccines we currently use and the protocols we recommend undergo unprecedented review.

  13. Dried influenza vaccines : Over the counter vaccines

    NARCIS (Netherlands)

    Saluja, Vinay; Hinrichs, Wouter L. J.; Frijlink, Henderik W.

    2010-01-01

    Since last year influenza pandemic has struck again after 40 years, this is the right moment to discuss the different available formulation options for influenza vaccine. Looking back to the last 4 decades, most vaccines are still formulated as liquid solution. These vaccines have shown a poor stabi

  14. Guillain-Barré Syndrome (GBS) and Flu Vaccine

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  15. Erythrocytic mobilization enhanced by the granulocyte colony-stimulating factor is associated with reduced anthrax-lethal-toxin-induced mortality in mice.

    Directory of Open Access Journals (Sweden)

    Hsin-Hou Chang

    Full Text Available Anthrax lethal toxin (LT, one of the primary virulence factors of Bacillus anthracis, causes anthrax-like symptoms and death in animals. Experiments have indicated that levels of erythrocytopenia and hypoxic stress are associated with disease severity after administering LT. In this study, the granulocyte colony-stimulating factor (G-CSF was used as a therapeutic agent to ameliorate anthrax-LT- and spore-induced mortality in C57BL/6J mice. We demonstrated that G-CSF promoted the mobilization of mature erythrocytes to peripheral blood, resulting in a significantly faster recovery from erythrocytopenia. In addition, combined treatment using G-CSF and erythropoietin tended to ameliorate B. anthracis-spore-elicited mortality in mice. Although specific treatments against LT-mediated pathogenesis remain elusive, these results may be useful in developing feasible strategies to treat anthrax.

  16. Pneumococcal Vaccines (PCV, PPSV)

    Science.gov (United States)

    ... or HIV infection); or cochlear implants. Why the Vaccines Are Recommended Children younger than 2 years old, adults over 65, ... of a pneumococcal vaccine or to the DTaP vaccine Caring for Your Child After Immunization These vaccines may cause mild fever ...

  17. Vaccine Basics (Smallpox)

    Science.gov (United States)

    ... this page: About CDC.gov . Smallpox About Smallpox History of Smallpox Spread and Eradication of Smallpox Transmission Signs and Symptoms Prevention and Treatment Smallpox Vaccine Basics Vaccine Safety Side Effects of Vaccination Who Should Get a Smallpox Vaccination? Bioterrorism The ...

  18. History of vaccination.

    Science.gov (United States)

    Plotkin, Stanley

    2014-08-26

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  19. Mucosal vaccination of fish

    NARCIS (Netherlands)

    Rombout, J.H.W.M.; Kiron, V.

    2014-01-01

    Among the novel vaccination methods, mucosal vaccination seems to possess all the desired criteria. The chapter reviews the state-of-the-art knowledge regarding this type of vaccination with a focus on their uptake, immune stimulation, and where possible, discusses their potential as future vaccines

  20. Overcoming Resistance to Change: An Analysis to the Department of Defense’s Anthrax Vaccine Immunization Program

    Science.gov (United States)

    2004-06-01

    strategies for overcoming resistance to change , in the midst of a proposed initiative that has become stalled as a result of mistrust and cynicism. The results...published similarities and differences in the areas Change Management, Organizational Change, Resistance to Change , Overcoming Resistance to Change , and

  1. Nucleic Acid Vaccines

    Institute of Scientific and Technical Information of China (English)

    LU Shan

    2004-01-01

    @@ Anew method of immunization was discovered in the early 1990s. Several research groups independently demonstrated that direct inoculation of DNA plasmids coding for a specific protein antigen could elicit immune responses against that antigen[1-4].Since in theory the mRNA molecules also have the potential to be translated into the protein antigen, this vaccination approach was officially named by WHO as the nucleic acid vaccination even though the term DNA vaccine has been used more commonly in the literature. This novel approach is considered the fourth generation of vaccines after live attenuated vaccines, killed or inactivated vaccines and recombinant protein based subunit vaccines.

  2. Vaccine adverse events.

    Science.gov (United States)

    Follows, Jill

    2012-01-01

    Millions of adults are vaccinated annually against the seasonal influenza virus. An undetermined number of individuals will develop adverse events to the influenza vaccination. Those who suffer substantiated vaccine injuries, disabilities, and aggravated conditions may file a timely, no-fault and no-cost petition for financial compensation under the National Vaccine Act in the Vaccine Court. The elements of a successful vaccine injury claim are described in the context of a claim showing the seasonal influenza vaccination was the cause of Guillain-Barré syndrome.

  3. Bacillus cereus G9241 Makes Anthrax Toxin and Capsule like Highly Virulent B. anthracis Ames but Behaves like Attenuated Toxigenic Nonencapsulated B. anthracis Sterne in Rabbits and Mice

    Science.gov (United States)

    2011-08-01

    Microbiology. All Rights Reserved. Bacillus cereus G9241 Makes Anthrax Toxin and Capsule like Highly Virulent B. anthracis Ames but Behaves like...G9241 for mice requires the presence of both plasmids. The Bacillus cereus group, of which Bacillus anthracis, Bacil- lus thuringiensis , and B... Bacillus cereus G9241 Makes Anthrax Toxin and Capsule like Highly Virulent B. anthracis Ames but Behaves like Attenuated Toxigenic Nonencapsulated B

  4. Vaccines against poverty

    OpenAIRE

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vacc...

  5. Facilitation of risk communication during the anthrax attacks of 2001: the organizational backstory.

    Science.gov (United States)

    Chess, Caron; Clarke, Lee

    2007-09-01

    The anthrax attacks of 2001 created risk communication problems that cannot be fully understood without appreciating the dynamics among organizations. Case studies of communication in New Jersey, consisting of interviews with a range of participants, found that existing organizational and professional networks facilitated trust among decisionmakers. This interpersonal trust improved communication among agencies and thereby risk communication with the public. For example, "white powder scares" were a problem even in places without contamination. Professionals' trust in each other was vital for responding productively. Conversely, organizational challenges, including conflict among agencies, hindered communication with key audiences. Although centralization and increased control are often seen as the remedy for communicative confusion, they also can quash the improvisational responses needed during crises.

  6. Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome.

    Directory of Open Access Journals (Sweden)

    Jonathan L Levinsohn

    Full Text Available NOD-like receptor (NLR proteins (Nlrps are cytosolic sensors responsible for detection of pathogen and danger-associated molecular patterns through unknown mechanisms. Their activation in response to a wide range of intracellular danger signals leads to formation of the inflammasome, caspase-1 activation, rapid programmed cell death (pyroptosis and maturation of IL-1β and IL-18. Anthrax lethal toxin (LT induces the caspase-1-dependent pyroptosis of mouse and rat macrophages isolated from certain inbred rodent strains through activation of the NOD-like receptor (NLR Nlrp1 inflammasome. Here we show that LT cleaves rat Nlrp1 and this cleavage is required for toxin-induced inflammasome activation, IL-1 β release, and macrophage pyroptosis. These results identify both a previously unrecognized mechanism of activation of an NLR and a new, physiologically relevant protein substrate of LT.

  7. Initiating informatics and GIS support for a field investigation of Bioterrorism: The New Jersey anthrax experience

    Directory of Open Access Journals (Sweden)

    Skinner Ric

    2003-11-01

    Full Text Available Abstract Background The investigation of potential exposure to anthrax spores in a Trenton, New Jersey, mail-processing facility required rapid assessment of informatics needs and adaptation of existing informatics tools to new physical and information-processing environments. Because the affected building and its computers were closed down, data to list potentially exposed persons and map building floor plans were unavailable from the primary source. Results Controlling the effects of anthrax contamination required identification and follow-up of potentially exposed persons. Risk of exposure had to be estimated from the geographic relationship between work history and environmental sample sites within the contaminated facility. To assist in establishing geographic relationships, floor plan maps of the postal facility were constructed in ArcView Geographic Information System (GIS software and linked to a database of personnel and visitors using Epi Info and Epi Map 2000. A repository for maintaining the latest versions of various documents was set up using Web page hyperlinks. Conclusions During public health emergencies, such as bioterrorist attacks and disease epidemics, computerized information systems for data management, analysis, and communication may be needed within hours of beginning the investigation. Available sources of data and output requirements of the system may be changed frequently during the course of the investigation. Integrating data from a variety of sources may require entering or importing data from a variety of digital and paper formats. Spatial representation of data is particularly valuable for assessing environmental exposure. Written documents, guidelines, and memos important to the epidemic were frequently revised. In this investigation, a database was operational on the second day and the GIS component during the second week of the investigation.

  8. Typhoid fever vaccination strategies.

    Science.gov (United States)

    Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

    2015-06-19

    Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control.

  9. Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA(-) (High Temperature Requirement A) Sterne Strain.

    Science.gov (United States)

    Chitlaru, Theodor; Israeli, Ma'ayan; Bar-Haim, Erez; Elia, Uri; Rotem, Shahar; Ehrlich, Sharon; Cohen, Ofer; Shafferman, Avigdor

    2016-01-06

    Anthrax is a lethal disease caused by the gram-positive spore-producing bacterium Bacillus anthracis. Live attenuated vaccines, such as the nonencapsulated Sterne strain, do not meet the safety standards mandated for human use in the Western world and are approved for veterinary purposes only. Here we demonstrate that disrupting the htrA gene, encoding the chaperone/protease HtrA (High Temperature Requirement A), in the virulent Bacillus anthracis Vollum strain results in significant virulence attenuation in guinea pigs, rabbits and mice, underlying the universality of the attenuated phenotype associated with htrA knockout. Accordingly, htrA disruption was implemented for the development of a Sterne-derived safe live vaccine compatible with human use. The novel B. anthracis SterneΔhtrA strain secretes functional anthrax toxins but is 10-10(4)-fold less virulent than the Sterne vaccine strain depending on animal model (mice, guinea pigs, or rabbits). In spite of this attenuation, double or even single immunization with SterneΔhtrA spores elicits immune responses which target toxaemia and bacteremia resulting in protection from subcutaneous or respiratory lethal challenge with a virulent strain in guinea pigs and rabbits. The efficacy of the immune-protective response in guinea pigs was maintained for at least 50 weeks after a single immunization.

  10. A heterodimer of a VHH (variable domains of camelid heavy chain-only) antibody that inhibits anthrax toxin cell binding linked to a VHH antibody that blocks oligomer formation is highly protective in an anthrax spore challenge model.

    Science.gov (United States)

    Moayeri, Mahtab; Leysath, Clinton E; Tremblay, Jacqueline M; Vrentas, Catherine; Crown, Devorah; Leppla, Stephen H; Shoemaker, Charles B

    2015-03-06

    Anthrax disease is caused by a toxin consisting of protective antigen (PA), lethal factor, and edema factor. Antibodies against PA have been shown to be protective against the disease. Variable domains of camelid heavy chain-only antibodies (VHHs) with affinity for PA were obtained from immunized alpacas and screened for anthrax neutralizing activity in macrophage toxicity assays. Two classes of neutralizing VHHs were identified recognizing distinct, non-overlapping epitopes. One class recognizes domain 4 of PA at a well characterized neutralizing site through which PA binds to its cellular receptor. A second neutralizing VHH (JKH-C7) recognizes a novel epitope. This antibody inhibits conversion of the PA oligomer from "pre-pore" to its SDS and heat-resistant "pore" conformation while not preventing cleavage of full-length 83-kDa PA (PA83) by cell surface proteases to its oligomer-competent 63-kDa form (PA63). The antibody prevents endocytosis of the cell surface-generated PA63 subunit but not preformed PA63 oligomers formed in solution. JKH-C7 and the receptor-blocking VHH class (JIK-B8) were expressed as a heterodimeric VHH-based neutralizing agent (VNA2-PA). This VNA displayed improved neutralizing potency in cell assays and protected mice from anthrax toxin challenge with much better efficacy than the separate component VHHs. The VNA protected virtually all mice when separately administered at a 1:1 ratio to toxin and protected mice against Bacillus anthracis spore infection. Thus, our studies show the potential of VNAs as anthrax therapeutics. Due to their simple and stable nature, VNAs should be amenable to genetic delivery or administration via respiratory routes.

  11. Nasal spray flu vaccine (image)

    Science.gov (United States)

    The flu vaccine can also be administered as a nasal spray instead of the usual injection method. It can be ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should not ...

  12. Vaccination: An Act of Love

    Science.gov (United States)

    ... benefits of vaccines. For this reason, we created Vaccination Week in the Americas to get vaccines to ... and no one gets left behind. Help the vaccination teams when they come to your town, your ...

  13. 2000~2009年广西炭疽流行病学分析%Epidemiological analysis of anthrax in Guangxi Province from 2000 to 2009

    Institute of Scientific and Technical Information of China (English)

    梁江明; 邓秋云; 曾竣; 廖驰真; 吴秀玲

    2011-01-01

    Aim To analyse the epidemiological features of anthrax in Guangxi Province from 2000 to 2009 and provide scientific basis for prevention and control of the disease. Methods The The data concerning prevalence and control of anthrax in Guangxi from 2000 to 2009 were collected and analyzed. Results The prevalence of anthrax occurred in Guangxi every year,and the prevalence of anthrax in livestock often frequently occurred prior to the epidemic in human beings. The anthrax in Guangxi was of the agricultural type and was widespread without apparent periodic characteristic,most of the anthrax eases were farmers and were infected by slaughtering and eating the sick livestock. The incidence of anthrax was from 0.0015/100 000 to 0.22/100 000 population. Most of the anthrax cases were cutaneous anthrax. Conclusion To educate people not slaughter or eat or sell sick livestock and process correctly the corpses of sick livestock are the key measures for prevention and control the anthrax..%目的 了解广西炭疽流行病学特征,为预防与控制本病提供科学依据.方法 对2000~2009年广西炭疽疫情报告及其相关资料进行回顾性分析.结果 广西炭疽病例每年均有发生.人间炭疽流行常继发于畜间炭疽流行,以局部暴发为主,流行类型属农业型,分布广泛.流行无明显的周期性,发病率在0.0015/10万~0.22/10万之间.受害者主要是农民,大多数都是由于剖食病死家畜而感染,以皮肤型炭疽最为多见.结论 认真做好炭疽防治知识的宣传教育工作.做到不剖杀、不分食、不出售病死家畜,并妥善处理好病死家畜尸体是防治本病的关键.

  14. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  15. Vaccines against poverty.

    Science.gov (United States)

    MacLennan, Calman A; Saul, Allan

    2014-08-26

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented.

  16. Vaccines and Immunization Practice.

    Science.gov (United States)

    Hogue, Michael D; Meador, Anna E

    2016-03-01

    Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

  17. Studies of the Biological and Molecular Basis of the Inhibition of Activity of Phagocytic Cells by Anthrax Toxin

    Science.gov (United States)

    1985-03-01

    activity of the anthrax toxin which could provide clues to the nature of its antiphagocytic effect and its contribution to virulence of B. anthracs...ccmponents makes this unlikely. Early observations on the nature of this toxin tended to emphasize the requirement for cooperative action of the three...with oxidizable substances in the ocmplex system. evidently, endogenous amines. especially taurine , are the most active of the available receptors, and

  18. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    Directory of Open Access Journals (Sweden)

    Kandadi Machender R

    2012-11-01

    Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

  19. Computational Modeling of Aerosol Hazard Arising from the Opening of an Anthrax Letter in an Open-Office Complex

    Science.gov (United States)

    Lien, F. S.; Ji, H.; Yee, E.

    Early experimental work, conducted at Defence R&D Canada — Suffield, measured and characterized the personal and environmental contamination associated with the simulated opening of anthrax-tainted letters under a number of different scenarios. A better understanding of the physical and biological processes is considerably significant for detecting, assessing, and formulating potential mitigation strategies for managing these risks. These preliminary experimental investigations have been extended to simulate the contamination from the opening of anthrax-tainted letters in an Open-Office environment using Computational Fluid Dynamics (CFD). Bacillus globigii (BG) was used as a biological simulant for anthrax, with 0.1 gram of the simulant released from opened letters in the experiments conducted. The accuracy of the model for prediction of the spatial distribution of BG spores in the office is first assessed quantitatively by comparison with measured SF6 concentrations (the baseline experiment), and then qualitatively by comparison with measured BG concentrations obtained under a number of scenarios, some involving people moving within various offices.

  20. MMR Vaccine (Measles, Mumps, and Rubella)

    Science.gov (United States)

    Attenuvax® Measles Vaccine ... R-Vax® II (as a combination product containing Measles Vaccine, Rubella Vaccine) ... M-R® II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)

  1. Vaccine Safety Datalink

    Science.gov (United States)

    The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.

  2. Vaccines in Multiple Sclerosis.

    Science.gov (United States)

    Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

    2016-04-01

    Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.

  3. Vaccines and Pregnancy

    Science.gov (United States)

    ... that pregnant women receive the seasonal inactivated flu vaccine (flu shot). Pregnant women are at an increased risk ... please see the MotherToBaby fact sheet Seasonal Influenza Vaccine (Flu Shot) during Pregnancy: https://mothertobaby.org/fact-sheets/ ...

  4. Generating memory with vaccination.

    Science.gov (United States)

    Castellino, Flora; Galli, Grazia; Del Giudice, Giuseppe; Rappuoli, Rino

    2009-08-01

    The goal of vaccination is to induce long-lasting protective immune memory. Although most vaccines induce good memory responses, the type of memory induced by different vaccines may be considerably different. In addition, memory responses to the same vaccine may be influenced by age, environmental and genetic factors. Results emerging from detailed and integrated profiling of immune-responses to natural infection or vaccination suggest that the type and duration of immune memory are largely determined by the magnitude and complexity of innate immune signals that imprint the acquired immune primary responses. Here we summarize results obtained from analyzing human immune memory responses to different types of vaccines. We will also discuss how extending clinical investigation to events occurring early after vaccination can help identify early predictive markers of protective memory and thus contribute to faster development of better and safer vaccines.

  5. The HPV Vaccination Crisis

    Science.gov (United States)

    Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.

  6. Vaccines in dermatology

    Directory of Open Access Journals (Sweden)

    Mitali M Shah

    2015-01-01

    Full Text Available A vaccine is a biological preparation that improves immunity to a specific disease. More than two centuries have passed since the first successful vaccine for smallpox was developed. We′ve come a long way since. Today′s vaccines are among the 21 st century′s most successful and cost-effective public health tools for preventing diseases.

  7. Efficacy of ETI-204 monoclonal antibody as an adjunct therapy in a New Zealand white rabbit partial survival model for inhalational anthrax.

    Science.gov (United States)

    Biron, Bethany; Beck, Katie; Dyer, David; Mattix, Marc; Twenhafel, Nancy; Nalca, Aysegul

    2015-04-01

    Inhalational anthrax is characterized by extensive bacteremia and toxemia as well as nonspecific to mild flu-like symptoms, until the onset of hypotension, shock, and mortality. Without treatment, the mortality rate approaches 100%. Antibiotic treatment is not always effective, and alternative treatments are needed, such as monotherapy for antibiotic-resistant inhalational anthrax or as an adjunct therapy in combination with antibiotics. The Bacillus anthracis antitoxin monoclonal antibody (MAb) ETI-204 is a high-affinity chimeric deimmunized antibody which targets the anthrax toxin protective antigen (PA). In this study, a partial protection New Zealand White (NZW) rabbit model was used to evaluate the protective efficacy of the adjunct therapy with the MAb. Following detection of PA in the blood, NZW rabbits were administered either an antibiotic (doxycycline) alone or the antibiotic in conjunction with ETI-204. Survival was evaluated to compare the efficacy of the combination adjunct therapy with that of an antibiotic alone in treating inhalational anthrax. Overall, the results from this study indicate that a subtherapeutic regimen consisting of an antibiotic in combination with an anti-PA MAb results in increased survival compared to the antibiotic alone and would provide an effective therapeutic strategy against symptomatic anthrax in nonvaccinated individuals.

  8. Brucellosis vaccines for livestock.

    Science.gov (United States)

    Goodwin, Zakia I; Pascual, David W

    2016-11-15

    Brucellosis is a livestock disease responsible for fetal loss due to abortions. Worldwide, this disease has profound economic and social impact by reducing the ability of livestock producers to provide an adequate supply of disease-free meat and dairy products. In addition to its presence in domesticated animals, brucellosis is harbored in a number of wildlife species creating new disease reservoirs, which adds to the difficulty of eradicating this disease. Broad and consistent use of the available vaccines would contribute in reducing the incidence of brucellosis. Unfortunately, this practice is not common. In addition, the current brucellosis vaccines cannot provide sterilizing immunity, and in certain circumstances, vaccinated livestock are not protected against co-mingling Brucella-infected wildlife. Given that these vaccines are inadequate for conferring complete protection for some vaccinated livestock, alternatives are being sought, and these include genetic modifications of current vaccines or their reformulations. Alternatively, many groups have sought to develop new vaccines. Subunit vaccines, delivered as a combination of soluble vaccine plus adjuvant or the heterologous expression of Brucella epitopes by different vaccine vectors are currently being tested. New live attenuated Brucella vaccines are also being developed and tested in their natural hosts. Yet, what is rarely considered is the route of vaccination which could improve vaccine efficacy. Since Brucella infections are mostly transmitted mucosally, mucosal delivery of a vaccine has the potential of eliciting a more robust protective immune response for improved efficacy. Hence, this review will examine these questions and provide the status of new vaccines for livestock brucellosis.

  9. Vaccination for Disease

    Science.gov (United States)

    Oehen, Stephan; Hengartner, Hans; Zinkernagel, Rolf M.

    1991-01-01

    Recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response. Some circumstances, however, were found in infections with a noncytopathic virus in which vaccination caused disease; sensitive parameters included the genetic background of the host, the time or dose of infection, and the constituents of the vaccine. Thus, immunopathologic damage by T cells may be an unwanted consequence of vaccination with the new types of peptide or recombinant vaccines that are being investigated for the human immunodeficiency viruses and other pathogens.

  10. Advances in FIV vaccine technology

    OpenAIRE

    Uhl, Elizabeth W.; Martin, Marcus; Coleman, James K.; Yamamoto, Janet K.

    2008-01-01

    Advances in vaccine technology are occurring in the molecular techniques used to develop vaccines and in the assessment of vaccine efficacy, allowing more complete characterization of vaccine-induced immunity correlating to protection. FIV vaccine development has closely mirrored and occasionally surpassed the development of HIV-1 vaccine, leading to first licensed technology. This review will discuss technological advances in vaccine designs, challenge infection assessment, and characterizat...

  11. Emerging Vaccine Informatics

    Directory of Open Access Journals (Sweden)

    Yongqun He

    2010-01-01

    Full Text Available Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO has been initiated to integrate various vaccine data and support automated reasoning.

  12. Vaccinations for pregnant women.

    Science.gov (United States)

    Swamy, Geeta K; Heine, R Phillips

    2015-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician-gynecologists are well suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and health care provider resources.

  13. Vaccines for allergy.

    Science.gov (United States)

    Linhart, Birgit; Valenta, Rudolf

    2012-06-01

    Vaccines aim to establish or strengthen immune responses but are also effective for the treatment of allergy. The latter is surprising because allergy represents a hyper-immune response based on immunoglobulin E production against harmless environmental antigens, i.e., allergens. Nevertheless, vaccination with allergens, termed allergen-specific immunotherapy is the only disease-modifying therapy of allergy with long-lasting effects. New forms of allergy diagnosis and allergy vaccines based on recombinant allergen-derivatives, peptides and allergen genes have emerged through molecular allergen characterization. The molecular allergy vaccines allow sophisticated targeting of the immune system and may eliminate side effects which so far have limited the use of traditional allergen extract-based vaccines. Successful clinical trials performed with the new vaccines indicate that broad allergy vaccination is on the horizon and may help to control the allergy pandemic.

  14. Development of a Zealand white rabbit deposition model to study inhalation anthrax.

    Science.gov (United States)

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E; Einstein, Daniel R; Kuprat, Andrew P; Corley, Richard A

    2016-01-01

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

  15. Differential dependence on N-glycosylation of anthrax toxin receptors CMG2 and TEM8.

    Directory of Open Access Journals (Sweden)

    Sarah Friebe

    Full Text Available ANTXR 1 and 2, also known as TEM8 and CMG2, are two type I membrane proteins, which have been extensively studied for their role as anthrax toxin receptors, but with a still elusive physiological function. Here we have analyzed the importance of N-glycosylation on folding, trafficking and ligand binding of these closely related proteins. We find that TEM8 has a stringent dependence on N-glycosylation. The presence of at least one glycan on each of its two extracellular domains, the vWA and Ig-like domains, is indeed necessary for efficient trafficking to the cell surface. In the absence of any N-linked glycans, TEM8 fails to fold correctly and is recognized by the ER quality control machinery. Expression of N-glycosylation mutants reveals that CMG2 is less vulnerable to sugar loss. The absence of N-linked glycans in one of the extracellular domains indeed has little impact on folding, trafficking or receptor function of the wild type protein expressed in tissue culture cells. N-glycans do, however, seem required in primary fibroblasts from human patients. Here, the presence of N-linked sugars increases the tolerance to mutations in cmg2 causing the rare genetic disease Hyaline Fibromatosis Syndrome. It thus appears that CMG2 glycosylation provides a buffer towards genetic variation by promoting folding of the protein in the ER lumen.

  16. Pharmacophore Selection and Redesign of Non-nucleotide Inhibitors of Anthrax Edema Factor

    Directory of Open Access Journals (Sweden)

    Maria Estrella Jimenez

    2012-11-01

    Full Text Available Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF, an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. The toxin’s basic activity is to convert ATP to cAMP, and it is thus in principle a simple phosphatase, which means that many mammalian enzymes, including intracellular adenylcyclases, may have a similar activity. While nucleotide based inhibitors, similar to its natural substrate, ATP, were identified early, these compounds had low activity and specificity for EF. We used a combined structural and computational approach to choose small organic molecules in large, web-based compound libraries that would, based on docking scores, bind to residues within the substrate binding pocket of EF. A family of fluorenone-based inhibitors was identified that inhibited the release of cAMP from cells treated with EF. The lead inhibitor was also shown to inhibit the diarrhea caused by enterotoxigenic E. coli (ETEC in a murine model, perhaps by serving as a quorum sensor. These inhibitors are now being tested for their ability to inhibit Anthrax infection in animal models and may have use against other pathogens that produce toxins similar to EF, such as Bordetella pertussis or Vibrio cholera.

  17. Incorporating retrospective clustering into a prospective Cusum methodology for anthrax: evaluating the effects of disease expectation.

    Science.gov (United States)

    Kracalik, Ian; Lukhnova, Larissa; Aikimbayev, Alim; Pazilov, Yerlan; Temiralyeva, Gulnara; Blackburn, Jason K

    2011-03-01

    We analysed livestock anthrax in Kazakhstan from 1960-2006, using a prospective CUSUM to examine the affects of expectation on the detection of spatio-temporal clusters. Three methods for deriving baselines were used for CUSUM; a standard z-score, AVG, a spatially-weighted z-score derived from Local Moran's I, LISA, and a moving-window average, MWA. LISA and AVG elicited alarm signals in the second year that did not return below threshold during the 47-year period, while MWA signaled an alarm at year four and relented at year fifteen. The number of spatial clusters elicited varied: LISA n=16, AVG n=11, and MWA n=3, although there were clusters present around Shymkent, in south-central Kazakhstan, in each method. The results illustrate that the selection of a baseline with an unknown background population has a significant effect on the ability to detect the onset of clusters in space and in time when employing a CUSUM methodology.

  18. Development of a Zealand white rabbit deposition model to study inhalation anthrax

    Energy Technology Data Exchange (ETDEWEB)

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, Andrew P.; Corley, Richard A.

    2016-01-28

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

  19. Diagnosis, treatment and prevention of anthrax%炭疽病的诊治和预防

    Institute of Scientific and Technical Information of China (English)

    徐婷婷; 沈叙庄; 杨永弘

    2003-01-01

    @@ 炭疽(Anthrax)是一种由炭疽杆菌(B. antracis)引起的人畜共患的急性传染病,主要发生在有蹄类哺乳动物,如牛、马、羊、猪、犬,人类通过直接或间接接触、吸入或食入病菌而致病.公元前300年希波克拉底就已描述此病,它曾经在全球范围出现暴发流行,因其本身的生物学特征及感染方式而被人们作为生物武器用于战争.2001年9月11日美国遭受恐怖主义袭击后,陆续出现炭疽感染患者,已确诊22名,11例为皮肤炭疽,11例为吸入性炭疽,9名吸入性炭疽患者曾经接触过装有炭疽杆菌的信件,其中6人死亡.因此我们有必要对该病深入了解.

  20. Lanthanide-functionalized silver nanoparticles for detection of an anthrax biomarker and test paper fabrication

    Science.gov (United States)

    Tan, Hongliang; Li, Qian; Ma, Chanjiao; Song, Yonghai; Xu, Fugang; Chen, Shouhui; Wang, Li

    2014-01-01

    It is highly desirable to develop a simple and sensitive analytical method for detection of anthrax biomarker (dipicolinic acid, DPA) because of its dangerous nature. In this work, we developed a fluorescent sensor for DPA detection based on terbium ion-functionalized silver nanoparticles with an average size of 6.7 nm (AgNPs-Tb3+). The fluorescent intensity of Tb-DPA complex on the surface of AgNPs was two times higher than that of Tb-DPA complex alone in a solution phase due to the metal-enhanced fluorescence (MEF) effect of AgNPs. The proposed fluorescent sensor exhibits excellent selectivity and high sensitivity for DPA. Importantly, a test paper for DPA detection was fabricated for the first time by the integration of AgNPs-Tb3+ onto the nitrocellulose membrane. Owing to the MEF effect of AgNPs, the lowest detectable concentration of the test paper-integrated AgNPs-Tb3+ for DPA by naked eyes is 10 times lower than that of the test paper-integrated Tb3+ alone. We believe that the presented strategy may open up new avenues to the development of portable and robust-sensing platforms based on functional hybrid materials.

  1. Rapid and label-free screening and identification of Anthrax simulants by Surface Enhanced Raman Spectroscopy

    Science.gov (United States)

    Lai, Antonia; Almaviva, Salvatore; Spizzichino, Valeria; Palucci, Antonio; Addari, Lorella; Luciani, Domenico; Mengali, Sandro; Marquette, Christophe; Berthuy, Ophélie; Jankiewicz, Bartlomiej; Pierno, Luigi

    2014-10-01

    In the framework of RAMBO (Rapid-Air Monitoring particle against biological threats) project of the European Defense Agency (EDA), the feasibility of an unattended Surface Enhanced Raman Spectroscopy (SERS) sensor for biological threats detection was investigated. Its main goal concern Bacillus anthrax detection, both as vegetative cells and endospores. However since such bacteria are classified in Risk Group 3 (very dangerous microorganism), Bacillus thuringiensis and Bacillus atrophaeus were used as simulants. In order to bind selectively the target bacilli, Phages properly selected were immobilized on an active commercially available SERS substrate (functionalization). The Phages are a type of virus that infect selectively, by means of receptors, specific bacteria. Moreover they can resist on water or air environments without losing their binding capabilities. The sensing surface was characterized by standard micro-Raman equipments to assess the background Raman features. The Raman measurements have been carried out from 10X to 100X of magnification to differentiate between average and local features. Moreover the fast response was acquired by limiting the measure time at less than 1 minute. Samples of vegetative cells and endospores of Bacilli were randomly dispersed on the functionalized SERS substrates. The results obtained are promising: samples with and without bacilli could be distinguished one from the other. This is a step toward the use of SERS as an effective and fast technique for early warning of biological threats.

  2. Cholera- and anthrax-like toxins are among several new ADP-ribosyltransferases.

    Directory of Open Access Journals (Sweden)

    Robert J Fieldhouse

    Full Text Available Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like toxin from Bacillus cereus, are among six new bacterial protein toxins we identified and characterized using in silico and cell-based techniques. We also uncovered medically relevant toxins from Mycobacterium avium and Enterococcus faecalis. We found agriculturally relevant toxins in Photorhabdus luminescens and Vibrio splendidus. These toxins belong to the ADP-ribosyltransferase family that has conserved structure despite low sequence identity. Therefore, our search for new toxins combined fold recognition with rules for filtering sequences--including a primary sequence pattern--to reduce reliance on sequence identity and identify toxins using structure. We used computers to build models and analyzed each new toxin to understand features including: structure, secretion, cell entry, activation, NAD+ substrate binding, intracellular target binding and the reaction mechanism. We confirmed activity using a yeast growth test. In this era where an expanding protein structure library complements abundant protein sequence data--and we need high-throughput validation--our approach provides insight into the newest toxin ADP-ribosyltransferases.

  3. The secret life of the anthrax agent Bacillus anthracis: bacteriophage-mediated ecological adaptations.

    Science.gov (United States)

    Schuch, Raymond; Fischetti, Vincent A

    2009-08-12

    Ecological and genetic factors that govern the occurrence and persistence of anthrax reservoirs in the environment are obscure. A central tenet, based on limited and often conflicting studies, has long held that growing or vegetative forms of Bacillus anthracis survive poorly outside the mammalian host and must sporulate to survive in the environment. Here, we present evidence of a more dynamic lifecycle, whereby interactions with bacterial viruses, or bacteriophages, elicit phenotypic alterations in B. anthracis and the emergence of infected derivatives, or lysogens, with dramatically altered survival capabilities. Using both laboratory and environmental B. anthracis strains, we show that lysogeny can block or promote sporulation depending on the phage, induce exopolysaccharide expression and biofilm formation, and enable the long-term colonization of both an artificial soil environment and the intestinal tract of the invertebrate redworm, Eisenia fetida. All of the B. anthracis lysogens existed in a pseudolysogenic-like state in both the soil and worm gut, shedding phages that could in turn infect non-lysogenic B. anthracis recipients and confer survival phenotypes in those environments. Finally, the mechanism behind several phenotypic changes was found to require phage-encoded bacterial sigma factors and the expression of at least one host-encoded protein predicted to be involved in the colonization of invertebrate intestines. The results here demonstrate that during its environmental phase, bacteriophages provide B. anthracis with alternatives to sporulation that involve the activation of soil-survival and endosymbiotic capabilities.

  4. The secret life of the anthrax agent Bacillus anthracis: bacteriophage-mediated ecological adaptations.

    Directory of Open Access Journals (Sweden)

    Raymond Schuch

    Full Text Available Ecological and genetic factors that govern the occurrence and persistence of anthrax reservoirs in the environment are obscure. A central tenet, based on limited and often conflicting studies, has long held that growing or vegetative forms of Bacillus anthracis survive poorly outside the mammalian host and must sporulate to survive in the environment. Here, we present evidence of a more dynamic lifecycle, whereby interactions with bacterial viruses, or bacteriophages, elicit phenotypic alterations in B. anthracis and the emergence of infected derivatives, or lysogens, with dramatically altered survival capabilities. Using both laboratory and environmental B. anthracis strains, we show that lysogeny can block or promote sporulation depending on the phage, induce exopolysaccharide expression and biofilm formation, and enable the long-term colonization of both an artificial soil environment and the intestinal tract of the invertebrate redworm, Eisenia fetida. All of the B. anthracis lysogens existed in a pseudolysogenic-like state in both the soil and worm gut, shedding phages that could in turn infect non-lysogenic B. anthracis recipients and confer survival phenotypes in those environments. Finally, the mechanism behind several phenotypic changes was found to require phage-encoded bacterial sigma factors and the expression of at least one host-encoded protein predicted to be involved in the colonization of invertebrate intestines. The results here demonstrate that during its environmental phase, bacteriophages provide B. anthracis with alternatives to sporulation that involve the activation of soil-survival and endosymbiotic capabilities.

  5. 抗炭疽毒素的小分子药物研究进展%Recent advances in development of small molecule inhibitors of anthrax toxin

    Institute of Scientific and Technical Information of China (English)

    刘家阔; 顾为; 聂爱华

    2011-01-01

    炭疽是由炭疽芽孢杆菌引起的一种人畜共患烈性传染病.炭疽菌主要通过释放炭疽毒素使宿主致病.炭疽毒素包括致死毒素和水肿毒素,这两种毒素是使炭疽感染者死亡的主要因素.该文综述了抗炭疽毒素小分子药物的研究进展.%Anthrax is a severe epidemic disease caused by Bacillus anthracis, and acts mainly by releasing anthrax toxin that consists of two toxins, lethal toxin (LT) and edema toxin (ET), which are the primary factors of death. In this review the recent advances in the development of small molecule inhibitors of anthrax toxin are discussed.

  6. Anthrax in cattle in southern Brazil: 1978-2006 Carbúnculo hemático em bovinos no sul do Brasil: 1978-2006

    Directory of Open Access Journals (Sweden)

    Ana Lucia Schild

    2006-12-01

    Full Text Available Ten outbreaks of anthrax occurred in cattle from 1978 to 2006 in southern Brazil, in 5 municipalities on the border with Uruguay, a country where the disease is frequent. The 10 outbreaks represented 0.2% of all bovine specimens received during the period by the Regional Diagnostic Laboratory of the Federal University of Pelotas, causing 267 deaths in a risk population of 6,605 head. The disease affected young and adult cattle mainly during summer. Only one farmer reported that sheep and horses were also affected. Clinically the peracute form was more frequent, but in some outbreaks the acute form with a clinical manifestation period of 6-48 hours was also observed. The source of infection was not established; but the reduced rainfall, associated with low, flat, flooded lands used for agriculture followed by animal grazing after harvest was probably related to the disease occurrence. Annual vaccination is an efficient way to prevent the disease.Foi realizado um estudo retrospectivo da ocorrência de carbúnculo hemático em bovinos na área de influência do Laboratório Regional de Diagnóstico (LRD da Faculdade de Veterinária da Universidade Federal de Pelotas. Entre 1978 e março de 2006, dez surtos da enfermidade ocorreram em cinco municípios da região sul do Rio Grande do Sul, todos localizados na fronteira com o Uruguai. A enfermidade representou 0,2% dos diagnósticos realizados no LRD no período. Ocorre em bovinos jovens e adultos, principalmente em verões quentes e secos, e com menor freqüência em outras épocas do ano. Freqüentemente, a doença se apresenta na forma hiperaguda, entretanto casos de carbúnculo hemático agudo podem ser observados. Não foi possível estabelecer a origem das infecções, mas precipitações pluviométricas menores que as normais, em campos planos, sujeitos a alagamentos freqüentes, utilizados para plantio e posterior uso das restevas (restolhos para a criação dos animais podem ter favorecido a

  7. Vaccine process technology.

    Science.gov (United States)

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

  8. Affinity binding of antibodies to supermacroporous cryogel adsorbents with immobilized protein A for removal of anthrax toxin protective antigen.

    Science.gov (United States)

    Ingavle, Ganesh C; Baillie, Les W J; Zheng, Yishan; Lis, Elzbieta K; Savina, Irina N; Howell, Carol A; Mikhalovsky, Sergey V; Sandeman, Susan R

    2015-05-01

    Polymeric cryogels are efficient carriers for the immobilization of biomolecules because of their unique macroporous structure, permeability, mechanical stability and different surface chemical functionalities. The aim of the study was to demonstrate the potential use of macroporous monolithic cryogels for biotoxin removal using anthrax toxin protective antigen (PA), the central cell-binding component of the anthrax exotoxins, and covalent immobilization of monoclonal antibodies. The affinity ligand (protein A) was chemically coupled to the reactive hydroxyl and epoxy-derivatized monolithic cryogels and the binding efficiencies of protein A, monoclonal antibodies to the cryogel column were determined. Our results show differences in the binding capacity of protein A as well as monoclonal antibodies to the cryogel adsorbents caused by ligand concentrations, physical properties and morphology of surface matrices. The cytotoxicity potential of the cryogels was determined by an in vitro viability assay using V79 lung fibroblast as a model cell and the results reveal that the cryogels are non-cytotoxic. Finally, the adsorptive capacities of PA from phosphate buffered saline (PBS) were evaluated towards a non-glycosylated, plant-derived human monoclonal antibody (PANG) and a glycosylated human monoclonal antibody (Valortim(®)), both of which were covalently attached via protein A immobilization. Optimal binding capacities of 108 and 117 mg/g of antibody to the adsorbent were observed for PANG attached poly(acrylamide-allyl glycidyl ether) [poly(AAm-AGE)] and Valortim(®) attached poly(AAm-AGE) cryogels, respectively, This indicated that glycosylation status of Valortim(®) antibody could significantly increase (8%) its binding capacity relative to the PANG antibody on poly(AAm-AGE)-protien-A column (p PBS through PANG or Valortim bound poly(AAm-AGE) cryogel were significantly (p PBS over 60 min of circulation. The high adsorption capacity towards anthrax toxin PA of the

  9. The 49th hour: analysis of a follow-up medication and vaccine dispensing field test.

    Science.gov (United States)

    Puerini, Raymond; Caum, Jessica; Francis, Natalie; Alles, Steven

    2015-01-01

    Anthrax response plans, exercises, and assessments over the past decade have focused almost exclusively on the first 48 hours of the public health response following a jurisdiction-wide exposure and provision of an initial 10-day supply of antibiotics from the Strategic National Stockpile (SNS). But mass dispensing of the subsequent 50-day course of antibiotics and administration of the 3-dose vaccine series have received considerably less attention, although these follow-up activities may prove even more complex. In 2014, the Philadelphia Department of Public Health (PDPH) made its first foray into this next frontier of mass prophylaxis planning by: (1) researching patient safety and adherence considerations relevant to the antibiotics in the SNS; (2) designing a model for a second-visit antibiotic and vaccine point of dispensing (POD), including development of an enhanced screening protocol that assumes a higher level of medical responsibility; and (3) field testing this model during a real seasonal influenza vaccination clinic to assess throughput and accuracy and to evaluate the resources needed to operationalize this model. While the observations and data presented here provide some framework for local long-term mass prophylaxis planning efforts, many areas remain undefined, including the distribution of responsibilities among the public health and healthcare communities to ensure patient safety. In addition to presenting findings, the larger intent of this article is to initiate a dialogue with other stakeholders at the local, state, and federal levels to advance long-term mass prophylaxis planning.

  10. Vaccine herd effect.

    Science.gov (United States)

    Kim, Tae Hyong; Johnstone, Jennie; Loeb, Mark

    2011-09-01

    Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible populations. The herd effect has had a major impact in the eradication of smallpox, has reduced transmission of pertussis, and protects against influenza and pneumococcal disease. A high uptake of vaccines is generally needed for success. In this paper we aim to provide an update review on the herd effect, focusing on the clinical benefit, by reviewing data for specific vaccines.

  11. Vaccines and Kawasaki disease.

    Science.gov (United States)

    Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

    2016-01-01

    The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

  12. Vaccination against seasonal flu

    CERN Document Server

    2015-01-01

    The Medical Service once again recommends you to get your annual flu vaccination for the year.   Vaccination is the most effective way of avoiding the illness and any serious consequences and protecting those around you. The flu can have especially serious consequences for people with chronic conditions (diabetes, cardio-vascular disease, etc.), pregnant women, infants, and people over 65 years of age. Remember, anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor) with their vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement by UNIQA. NB: The Medical Service cannot provide this vaccination service for family members or retired members of the personnel. For more information: • The "Seasonal flu" flyer by the Medical Service • Recommendations of the Swiss Federal Office of Public...

  13. Vaccination and neurological disorders

    Directory of Open Access Journals (Sweden)

    Anastasia Gkampeta

    2015-12-01

    Full Text Available Active immunization of children has been proven very effective in elimination of life threatening complications of many infectious diseases in developed countries. However, as vaccination-preventable infectious diseases and their complications have become rare, the interest focuses on immunization-related adverse reactions. Unfortunately, fear of vaccination-related adverse effects can led to decreased vaccination coverage and subsequent epidemics of infectious diseases. This review includes reports about possible side effects following vaccinations in children with neurological disorders and also published recommendations about vaccinating children with neurological disorders. From all international published data anyone can conclude that vaccines are safer than ever before, but the challenge remains to convey this message to society.

  14. 2011年四川省炭疽个案调查%Survey of Anthrax Cases in Sichuan Province

    Institute of Scientific and Technical Information of China (English)

    李帆; 汪立茂; 吴朝学; 魏敏; 祁腾

    2013-01-01

    Objective To analyze pathogenic characteristics of anthrax of Sichuan province in 2011, and to provide scientific basis for future prevention work. Methods All cases reported from network in 2011 were statistically analyzed with respects of onset date and current addresses. Results A total of 86 anthrax cases were reported and all were skin anthrax, and the male accounted for 69. 77% , significantly more than women; the pas-toralist was the dominating occupation (72. 09% ), followed by the farmers (19. 77% ). The average age was 39. 12, and the onsets were mainly young adults. The onset peak appeared in July to September of the year, contacting, striping and eating dead animals were the main sources of infection (61. 63% ); and contacting was the main infection modus (98. 84% ). Conclusion Contacting, striping and eating dead animals has become primary means of human anthrax infections. The work of health education and livestock epidemic control should be enhanced.%目的 分析四川省2011年炭疽病例发病特征,为今后的防治工作提供依据.方法 收集整理2011年所有通过网络报告病例的个案调查表,按发病日期和现住址进行统计分析.结果 2011年全省共报告炭疽病例86例,均为皮肤型炭疽;男性占69.77%,明显多于女性;职业以牧民为主(72.09%),其次为农民(19.77%);平均年龄39.12岁,青壮年发病较多;发病高峰出现在7~9月;接触、剥食病死动物是最主要的感染来源(61.63%),接触感染是主要的感染方式(98.84%).结论 2011年四川省炭疽病例主要为青壮年男性,剥食和接触病死动物成为引起人间炭疽的感染的主要方式,应加强健康教育和畜间疫情的控制力度.

  15. Vaccine Treatment for Prostate Cancer

    Science.gov (United States)

    ... Back After Treatment Prostate Cancer Treating Prostate Cancer Vaccine Treatment for Prostate Cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  16. HIV/AIDS and Vaccines

    Science.gov (United States)

    ... against the disease. Is There a Vaccine for HIV? No. There is currently no vaccine that will ... in this video! /* // ** // */ Why Do We Need an HIV Vaccine? Today, more people living with HIV than ...

  17. Influenza Vaccine, Inactivated or Recombinant

    Science.gov (United States)

    ... die from flu, and many more are hospitalized.Flu vaccine can:keep you from getting flu, make flu ... inactivated or recombinant influenza vaccine?A dose of flu vaccine is recommended every flu season. Children 6 months ...

  18. Liver Disease and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  19. Renal Disease and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  20. HIV Infection and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals HIV Infection and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... percentage is less than 15%. Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  1. Vaccines for Drug Abuse

    Science.gov (United States)

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2012-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

  2. Alphavirus replicon vaccines.

    Science.gov (United States)

    Vander Veen, Ryan L; Harris, D L Hank; Kamrud, Kurt I

    2012-06-01

    The alphavirus replicon technology has been utilized for many years to develop vaccines for both veterinary and human applications. Many developments have been made to the replicon platform recently, resulting in improved safety and efficacy of replicon particle (RP) vaccines. This review provides a broad overview of the replicon technology and safety features of the system and discusses the current literature on RP and replicon-based vaccines.

  3. Epidemiological analysis of anthrax in Gansu Province from 2005 to 2011%2005-2011年甘肃省炭疽流行病学分析

    Institute of Scientific and Technical Information of China (English)

    刘东鹏; 刘新凤; 魏孔福; 杨建军

    2012-01-01

    目的 分析甘肃省近年炭疽流行病学特征,为制定防制策略提供科学依据.方法 对甘肃2005-2011年炭疽疫情报告情况及相关资料进行回顾性分析.结果 7年来甘肃省每年均有炭疽病例发生,累计报告发病306例,发病率在0.07/10万~0.25/10万之间波动,年平均发病率为0.17/10万;具有一定的地域性特征,主要发病在牧区,甘南州发病率最高(4.88/10万);发病季节多见于夏秋季的6-9月,占总发病数的54.58%;男性(67.65%)多于女性(32.35%),年龄以青壮年为主;以皮肤型炭疽最为多见,占98.37%.结论 甘肃省仍然是我国炭疽高发省份之一;认真做好炭疽防治知识的宣传教育工作,加强相关部门间合作,及时发现并处理疫情是防治本病的重要措施.%Objective To analyze the epidemiological features of anthrax in Gansu Province, and provide scientific evidence for developing preventive and control strategies. Methods The dada of anthrax epidemic in Cansu Province from 2005 to 2011 was analyzed by using retrospective study. Results The cases of anthrax occurred in Gansu Province every year in recent seven years, and there were totally 306 cases of anthrax. The incidence of anthrax was 0. 17/105 on average, and all incidences waved between 0. 07/10 to 0. 25/10 . Major anthrax cases occurred in pastoral areas, and the highest incidence area was Gannan (4. 88/105). Anthrax was more common during June to September in summer and autumn, accounting for 54.58% of total cases. The incidence in males (67.65%) was higher than that in females (32. 35% ) , and main in youth people. Cutaneous anthrax was the most common (98. 37% ) type. Conclusion Gansu is still one of the provinces with high incidence of anthrax in China. Health education on anthrax prevention and treatment, strengthening cooperation among related departments, identifying and controlling epidemics on time are the key measures for prevention and control on anthrax.

  4. Developing vaccines against pandemic influenza.

    OpenAIRE

    Wood, J M

    2001-01-01

    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illust...

  5. Vaccines, our shared responsibility.

    Science.gov (United States)

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-05

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases.

  6. Dengue virus vaccine development.

    Science.gov (United States)

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches.

  7. Differential Function of Lip Residues in the Mechanism and Biology of an Anthrax Hemophore

    Energy Technology Data Exchange (ETDEWEB)

    Ekworomadu, MarCia T.; Poor, Catherine B.; Owens, Cedric P.; Balderas, Miriam A.; Fabian, Marian; Olson, John S.; Murphy, Frank; Balkabasi, Erol; Honsa, Erin S.; He, Chuan; Goulding, Celia W.; Maresso, Anthony W. (Baylor); (UCI); (Cornell); (Rice); (UC)

    2014-10-02

    To replicate in mammalian hosts, bacterial pathogens must acquire iron. The majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. Pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin. Bacillus anthracis, the causative agent of anthrax disease, secretes two hemophores, IsdX1 and IsdX2, to acquire heme from host hemoglobin and enhance bacterial replication in iron-starved environments. Both proteins contain NEAr-iron Transporter (NEAT) domains, a conserved protein module that functions in heme acquisition in Gram-positive pathogens. Here, we report the structure of IsdX1, the first of a Gram-positive hemophore, with and without bound heme. Overall, IsdX1 forms an immunoglobin-like fold that contains, similar to other NEAT proteins, a 3{sub 10}-helix near the heme-binding site. Because the mechanistic function of this helix in NEAT proteins is not yet defined, we focused on the contribution of this region to hemophore and NEAT protein activity, both biochemically and biologically in cultured cells. Site-directed mutagenesis of amino acids in and adjacent to the helix identified residues important for heme and hemoglobin association, with some mutations affecting both properties and other mutations affecting only heme stabilization. IsdX1 with mutations that reduced the ability to associate with hemoglobin and bind heme failed to restore the growth of a hemophore-deficient strain of B. anthracis on hemoglobin as the sole iron source. These data indicate that not only is the 3{sub 10}-helix important for NEAT protein biology, but also that the processes of hemoglobin and heme binding can be both separate as well as coupled, the latter function being necessary for maximal heme-scavenging activity. These studies enhance our understanding of NEAT domain and hemophore function and set the stage for structure-based inhibitor design to block NEAT domain interaction with

  8. Designing HER2 vaccines.

    Science.gov (United States)

    Foy, Teresa M; Fanger, Gary R; Hand, Susan; Gerard, Catherine; Bruck, Claudine; Cheever, Martin A

    2002-06-01

    HER2/neu is a compelling cancer vaccine candidate because it is overexpressed on some cancer cells relative to normal tissues, it is known to be immunogenic in both animal models and in humans, and it is already known to be targetable by the antibody component of the immune system in the form of monoclonal antibody therapy with trastuzumab. Vaccines offer the theoretical advantage of being able to elicit T-cell responses in addition to antibody responses. HER2 vaccines have been shown to provide benefit in animal models and to be immunogenic in humans. However, the optimal vaccine formulation is not yet known and the therapeutic efficacy of the vaccines in humans has not yet been evaluated. HER2 vaccine approaches currently being tested include peptide-based, DNA plasmid-based, and protein-based vaccines. Our group has developed and started testing a protein-based vaccine composed of both the extracellular domain of HER2 and the carboxyl terminal autophosphorylation portion of the intracellular domain. The extracellular domain was retained to provide for antibody targeting. The kinase domain of the intracellular domain was excluded because of its high degree of homology to other human kinases. The carboxyl terminal autophosphorylation domain was retained because it is the most unique and possibly most immunogenic portion of the HER2 molecule with the least homology to other members of the HER family. The vaccine, termed dHER2, is immunogenic in mice and primates. In animal models it can elicit CD8 and CD4 T-cell responses as well as antibody responses that suppress the growth of HER2-positive cancer cells in vitro and in vivo. Vaccine trials are contemplated in patients with breast cancer that will determine whether the vaccine construct is similarly immunogenic in humans.

  9. Clinical development of Ebola vaccines.

    Science.gov (United States)

    Sridhar, Saranya

    2015-09-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines.

  10. Epidemiological Investigation of Cutaneous Anthrax Outbreak%皮肤炭疽疫情的流行病学调查

    Institute of Scientific and Technical Information of China (English)

    任丽云

    2015-01-01

    某地自6月25日~7月5日累计发生4例皮肤炭疽病例。疫情发生后,采取了隔离治疗病人为主的综合性治疗措施,控制了疫情的发展。根据患者的临床表现、流行病学调查以及患者的病原学检测结果,认为此起事件是由病死牛传播引起的皮肤炭疽疫情。按照《省突发公共卫生事件应急预案》的规定符合一般突发公共卫生事件的标准,启动Ⅳ级应急响应。%A place from June 25 - July 5 cumulative four cases of cutaneous anthrax cases have occurred. After the out-break, taking the isolation and treatment of patients based integrated treatment measures to control the development of the epidemic. According to clinical manifestations, epidemiology and etiology of the patient's test results that this incident was cutaneous anthrax epidemic caused by the spread of cattle died. In accordance with the"provincial public health emergency contingency plan" in line with the provisions of the general standard of public health emergencies, start Ⅳ level emergency response.

  11. Secretory expression and efficient purification of recombinant anthrax toxin lethal factor with full biological activity in E. coli.

    Science.gov (United States)

    Liu, Ju; Cai, Chenguang; Guo, Qiang; Zhang, Jun; Dong, Dayong; Li, Guanlin; Fu, Ling; Xu, Junjie; Chen, Wei

    2013-05-01

    Lethal factor (LF), a virulence factor of Bacillus anthracis, plays key roles in anthrax pathogenesis and host-pathogen interactions. The detailed mechanisms by which LF contributes to infection are still under investigation. While these studies require pure, homogeneous and reliable LF preparations, most methods reported for production of recombinant LF (rLF) in B. anthracis or Escherichia coli either are complicated or add extra residues to the protein. In this work, we modified our previous method by codon optimization and chromatograph workflow refinement and developed an improved strategy for efficient production of rLF from the periplasm of E. coli. We were able to obtain fully functional rLF with a purity above 95% and with a considerable yield of 5 mg/L. The preparation was characterized by SDS-PAGE, Western blot, and N-terminal sequencing, and the activity was validated by intoxication of macrophages and Fischer 344 rats. Our final product is suitable for most research involving drug development and mechanism analysis of anthrax pathogenesis.

  12. Cytolethal distending toxin B as a cell-killing component of tumor-targeted anthrax toxin fusion proteins.

    Science.gov (United States)

    Bachran, C; Hasikova, R; Leysath, C E; Sastalla, I; Zhang, Y; Fattah, R J; Liu, S; Leppla, S H

    2014-01-16

    Cytolethal distending toxin (Cdt) is produced by Gram-negative bacteria of several species. It is composed of three subunits, CdtA, CdtB, and CdtC, with CdtB being the catalytic subunit. We fused CdtB from Haemophilus ducreyi to the N-terminal 255 amino acids of Bacillus anthracis toxin lethal factor (LFn) to design a novel, potentially potent antitumor drug. As a result of this fusion, CdtB was transported into the cytosol of targeted cells via the efficient delivery mechanism of anthrax toxin. The fusion protein efficiently killed various human tumor cell lines by first inducing a complete cell cycle arrest in the G2/M phase, followed by induction of apoptosis. The fusion protein showed very low toxicity in mouse experiments and impressive antitumor effects in a Lewis Lung carcinoma model, with a 90% cure rate. This study demonstrates that efficient drug delivery by a modified anthrax toxin system combined with the enzymatic activity of CdtB has great potential as anticancer treatment and should be considered for the development of novel anticancer drugs.

  13. Bacillus cereus Biovar Anthracis Causing Anthrax in Sub-Saharan Africa—Chromosomal Monophyly and Broad Geographic Distribution

    Science.gov (United States)

    Mabon, Philip; Zimmermann, Fee; Lankester, Felix; Peller, Tianna; Feistner, Anna; Todd, Angelique; Herbinger, Ilka; de Nys, Hélène M.; Muyembe-Tamfun, Jean-Jacques; Karhemere, Stomy; Wittig, Roman M.; Couacy-Hymann, Emmanuel; Grunow, Roland; Calvignac-Spencer, Sébastien; Corbett, Cindi R.; Klee, Silke R.; Leendertz, Fabian H.

    2016-01-01

    Through full genome analyses of four atypical Bacillus cereus isolates, designated B. cereus biovar anthracis, we describe a distinct clade within the B. cereus group that presents with anthrax-like disease, carrying virulence plasmids similar to those of classic Bacillus anthracis. We have isolated members of this clade from different mammals (wild chimpanzees, gorillas, an elephant and goats) in West and Central Africa (Côte d’Ivoire, Cameroon, Central African Republic and Democratic Republic of Congo). The isolates shared several phenotypic features of both B. anthracis and B. cereus, but differed amongst each other in motility and their resistance or sensitivity to penicillin. They all possessed the same mutation in the regulator gene plcR, different from the one found in B. anthracis, and in addition, carry genes which enable them to produce a second capsule composed of hyaluronic acid. Our findings show the existence of a discrete clade of the B. cereus group capable of causing anthrax-like disease, found in areas of high biodiversity, which are possibly also the origin of the worldwide distributed B. anthracis. Establishing the impact of these pathogenic bacteria on threatened wildlife species will require systematic investigation. Furthermore, the consumption of wildlife found dead by the local population and presence in a domestic animal reveal potential sources of exposure to humans. PMID:27607836

  14. 一例肺炭疽死亡病例的流行病学调查分析%Epidemiological survey of death case of pulmonary anthrax

    Institute of Scientific and Technical Information of China (English)

    陈卫民; 刘丹

    2012-01-01

    2011年8月内蒙古自治区乌兰浩特市发生一起炭疽死亡病例疫情.采用流行病学调查、噬菌体裂解实验及青霉素敏感实验进行分析和诊断.共确诊6例病例,其中5例皮肤炭疽病例治疗痊愈,1例肺炭疽死亡.患者有明确的病、死畜接触史.通过对感染病畜肉的追踪销毁、接触人群的隔离检查及患者接触环境的消毒,及时有效地控制了病情的发展.%To understand the epidemiological characteristics of 1 death case of pulmonary anthrax and provide scientific evidence for developing prevention and control measures. Epidemiological survey, bacteriophage lyric test and penicillin-sensitive test were conducted. Among 6 anthrax cases diagnosed, 5 cases of cutaneous anthrax recovered after treatment, 1 cases of pulmonary anthrax died. The death case had obvious contact with sick and dead livestock. The epidemic was effectively controlled by tracing and destroying of sick livestock neat, isolation of close contacts and environment disinfection.

  15. Assessment of Neutralising Activity of Colostrum-Derived, Polyclonal, Bovine Antibodies: Use of the J774A.1 Anthrax Lethal Toxin Cytototoxity Assay

    Science.gov (United States)

    2005-12-01

    Assessment of Neutralising Activity of Colostrum - Derived, Polyclonal, Bovine Antibodies: Use of the J774A.1 Anthrax Lethal Toxin...activity of colostrum -derived, polyclonal, bovine antibodies. Antibodies against lethal factor and protective antigen were found to protect...APPROVED FOR PUBLIC RELEASE Assessment of Neutralising Activity of Colostrum - Derived, Polyclonal, Bovine Antibodies: Use of the J774A.1

  16. Childhood Vaccine Schedule

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... as pneumonia, blood infections, and bacterial meningitis Rotavirus vaccine (three ... in babies and young children 4 Months DTaP, Hib, IPV, PCV, RV 6 ...

  17. Vaccines and autoimmunity.

    Science.gov (United States)

    Agmon-Levin, Nancy; Paz, Ziv; Israeli, Eitan; Shoenfeld, Yehuda

    2009-11-01

    Vaccines have been used for over 200 years and are the most effective way of preventing the morbidity and mortality associated with infections. Like other drugs, vaccines can cause adverse events, but unlike conventional medicines, which are prescribed to people who are ill, vaccines are administered to healthy individuals, thus increasing the concern over adverse reactions. Most side effects attributed to vaccines are mild, acute and transient; however, rare reactions such as hypersensitivity, induction of infection, and autoimmunity do occur and can be severe and even fatal. The rarity and subacute presentation of post-vaccination autoimmune phenomena means that ascertaining causality between these events can be difficult. Moreover, the latency period between vaccination and autoimmunity ranges from days to years. In this article, on the basis of published evidence and our own experience, we discuss the various aspects of the causal and temporal interactions between vaccines and autoimmune phenomena, as well as the possible mechanisms by which different components of vaccines might induce autoimmunity.

  18. Vaccines and autoimmunity.

    Science.gov (United States)

    De Martino, M; Chiappini, E; Galli, L

    2013-01-01

    Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases.

  19. Towards universal influenza vaccines?

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); G.F. Rimmelzwaan (Guus)

    2011-01-01

    textabstractVaccination is the most cost-effective way to reduce the considerable disease burden of seasonal influenza. Although seasonal influenza vaccines are effective, their performance in the elderly and immunocompromised individuals would benefit from improvement. Major problems related to the

  20. Pricing of new vaccines.

    Science.gov (United States)

    Lee, Bruce Y; McGlone, Sarah M

    2010-08-01

    New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following ten components: 1. Conduct a target population analysis; 2. Map potential competitors and alternatives; 3. Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; 4. Quantify the incremental value of the new vaccine's characteristics; 5. Determine vaccine positioning in the marketplace; 6. Estimate the vaccine price-demand curve; 7. Calculate vaccine costs (including those of manufacturing, distribution, and research and development); 8. Account for various legal, regulatory, third party payer, and competitor factors; 9. Consider the overall product portfolio; 10. Set pricing objectives; 11. Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area.

  1. Trends in vaccine adjuvants

    NARCIS (Netherlands)

    Schijns, V.E.J.C.; Lavelle, E.C.

    2011-01-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a

  2. Conscientious Objection to Vaccination.

    Science.gov (United States)

    Clarke, Steve; Giubilini, Alberto; Walker, Mary Jean

    2017-03-01

    Vaccine refusal occurs for a variety of reasons. In this article we examine vaccine refusals that are made on conscientious grounds; that is, for religious, moral, or philosophical reasons. We focus on two questions: first, whether people should be entitled to conscientiously object to vaccination against contagious diseases (either for themselves or for their children); second, if so, to what constraints or requirements should conscientious objection (CO) to vaccination be subject. To address these questions, we consider an analogy between CO to vaccination and CO to military service. We argue that conscientious objectors to vaccination should make an appropriate contribution to society in lieu of being vaccinated. The contribution to be made will depend on the severity of the relevant disease(s), its morbidity, and also the likelihood that vaccine refusal will lead to harm. In particular, the contribution required will depend on whether the rate of CO in a given population threatens herd immunity to the disease in question: for severe or highly contagious diseases, if the population rate of CO becomes high enough to threaten herd immunity, the requirements for CO could become so onerous that CO, though in principle permissible, would be de facto impermissible.

  3. Vaccination: Who Should Do It, Who Should Not and Who Should Take Precautions

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  4. DNA fusion gene vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup

    2010-01-01

    DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... with viral-vectored vaccines, various synergistic components may need to be incorporated into DNA vaccines. From the perspective of the future clinical use of DNA vaccines, it has been suggested that antigen presentation should be improved and cytokine coadministration attempted. However, even...

  5. Diseases and vaccines

    DEFF Research Database (Denmark)

    Andersen, Nina Blom; Almlund, Pernille

    2012-01-01

    between authorities, politicians, media and citizens. On the contrary, no broad commitment about the offer of a new pandemic vaccine to individuals from e.g. at-risk groups was reached. The vaccine was characterized by considerable uncertainty with regard to effects and side effects and many people...... considered the vaccine as risky and a threat more severe than the influenza. The health authorities? communication was more unclear on this question, confusion increased in the Danish population and more critical voices were raised. This uncertain communication about the vaccines? effects and side effects...... and the critical voices in the population are widespread in communication about vaccines in general and an increasing number of people are expressing skepticism and deselect this product. The communication processes are seen as a typical example of the difficulties of communicating science and risk and show how...

  6. Against vaccine assay secrecy.

    Science.gov (United States)

    Herder, Matthew; Hatchette, Todd F; Halperin, Scott A; Langley, Joanne M

    2015-01-01

    Increasing the transparency of the evidence base behind health interventions such as pharmaceuticals, biologics, and medical devices, has become a major point of critique, conflict, and policy focus in recent years. Yet the lack of publicly available information regarding the immunogenicity assays upon which many important, widely used vaccines are based has received no attention to date. In this paper we draw attention to this critical public health problem by reporting on our efforts to secure vaccine assay information in respect of 10 vaccines through Canada's access to information law. We argue, under Canadian law, that the public health interest in having access to the methods for these laboratory procedures should override claims by vaccine manufacturers and regulators that this information is proprietary; and, we call upon several actors to take steps to ensure greater transparency with respect to vaccine assays, including regulators, private firms, researchers, research institutions, research funders, and journal editors.

  7. Against vaccine assay secrecy

    Science.gov (United States)

    Herder, Matthew; Hatchette, Todd F; Halperin, Scott A; Langley, Joanne M

    2015-01-01

    Increasing the transparency of the evidence base behind health interventions such as pharmaceuticals, biologics, and medical devices, has become a major point of critique, conflict, and policy focus in recent years. Yet the lack of publicly available information regarding the immunogenicity assays upon which many important, widely used vaccines are based has received no attention to date. In this paper we draw attention to this critical public health problem by reporting on our efforts to secure vaccine assay information in respect of 10 vaccines through Canada's access to information law. We argue, under Canadian law, that the public health interest in having access to the methods for these laboratory procedures should override claims by vaccine manufacturers and regulators that this information is proprietary; and, we call upon several actors to take steps to ensure greater transparency with respect to vaccine assays, including regulators, private firms, researchers, research institutions, research funders, and journal editors. PMID:25826194

  8. Neisseria meningitidis B vaccines.

    Science.gov (United States)

    Panatto, Donatella; Amicizia, Daniela; Lai, Piero Luigi; Gasparini, Roberto

    2011-09-01

    Invasive infections caused by Neisseria meningitidis are a serious public health problem worldwide and have a heavy economic impact. The incidence of invasive disease due to Neisseria meningitidis is highly variable according to geographical area and serogroup distribution. Since the introduction of vaccination programs with conjugated vaccine C in children and adolescents, most cases of invasive meningococcal disease in developed countries have been caused by meningococcus B. It is important to underline that invasive meningococcal disease will not be controlled until safe and effective vaccines for meningococcal B are available and widely used. The aims of this article are to describe the most recent developments in meningococcal B vaccines and to discuss how these vaccines can contribute to containing meningococcal disease.

  9. Vaccine safety--vaccine benefits: science and the public's perception.

    Science.gov (United States)

    Wilson, C B; Marcuse, E K

    2001-11-01

    The development of cowpox vaccination by Jenner led to the development of immunology as a scientific discipline. The subsequent eradication of smallpox and the remarkable effects of other vaccines are among the most important contributions of biomedical science to human health. Today, the need for new vaccines has never been greater. However, in developed countries, the public's fear of vaccine-preventable diseases has waned, and awareness of potential adverse effects has increased, which is threatening vaccine acceptance. To further the control of disease by vaccination, we must develop safe and effective new vaccines to combat infectious diseases, and address the public's concerns.

  10. Vaccines for canine leishmaniasis

    Directory of Open Access Journals (Sweden)

    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  11. The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

    Science.gov (United States)

    McNeil, Michael M; Gee, Julianne; Weintraub, Eric S; Belongia, Edward A; Lee, Grace M; Glanz, Jason M; Nordin, James D; Klein, Nicola P; Baxter, Roger; Naleway, Allison L; Jackson, Lisa A; Omer, Saad B; Jacobsen, Steven J; DeStefano, Frank

    2014-09-22

    The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods.

  12. Cross-reactivity of anthrax and C2 toxin: protective antigen promotes the uptake of botulinum C2I toxin into human endothelial cells.

    Directory of Open Access Journals (Sweden)

    Angelika Kronhardt

    Full Text Available Binary toxins are among the most potent bacterial protein toxins performing a cooperative mode of translocation and exhibit fatal enzymatic activities in eukaryotic cells. Anthrax and C2 toxin are the most prominent examples for the AB(7/8 type of toxins. The B subunits bind both host cell receptors and the enzymatic A polypeptides to trigger their internalization and translocation into the host cell cytosol. C2 toxin is composed of an actin ADP-ribosyltransferase (C2I and C2II binding subunits. Anthrax toxin is composed of adenylate cyclase (EF and MAPKK protease (LF enzymatic components associated to protective antigen (PA binding subunit. The binding and translocation components anthrax protective antigen (PA(63 and C2II of C2 toxin share a sequence homology of about 35%, suggesting that they might substitute for each other. Here we show by conducting in vitro measurements that PA(63 binds C2I and that C2II can bind both EF and LF. Anthrax edema factor (EF and lethal factor (LF have higher affinities to bind to channels formed by C2II than C2 toxin's C2I binds to anthrax protective antigen (PA(63. Furthermore, we could demonstrate that PA in high concentration has the ability to transport the enzymatic moiety C2I into target cells, causing actin modification and cell rounding. In contrast, C2II does not show significant capacity to promote cell intoxication by EF and LF. Together, our data unveiled the remarkable flexibility of PA in promoting C2I heterologous polypeptide translocation into cells.

  13. The genome of a Bacillus isolate causing anthrax in chimpanzees combines chromosomal properties of B. cereus with B. anthracis virulence plasmids.

    Directory of Open Access Journals (Sweden)

    Silke R Klee

    Full Text Available Anthrax is a fatal disease caused by strains of Bacillus anthracis. Members of this monophyletic species are non motile and are all characterized by the presence of four prophages and a nonsense mutation in the plcR regulator gene. Here we report the complete genome sequence of a Bacillus strain isolated from a chimpanzee that had died with clinical symptoms of anthrax. Unlike classic B. anthracis, this strain was motile and lacked the four prohages and the nonsense mutation. Four replicons were identified, a chromosome and three plasmids. Comparative genome analysis revealed that the chromosome resembles those of non-B. anthracis members of the Bacillus cereus group, whereas two plasmids were identical to the anthrax virulence plasmids pXO1 and pXO2. The function of the newly discovered third plasmid with a length of 14 kbp is unknown. A detailed comparison of genomic loci encoding key features confirmed a higher similarity to B. thuringiensis serovar konkukian strain 97-27 and B. cereus E33L than to B. anthracis strains. For the first time we describe the sequence of an anthrax causing bacterium possessing both anthrax plasmids that apparently does not belong to the monophyletic group of all so far known B. anthracis strains and that differs in important diagnostic features. The data suggest that this bacterium has evolved from a B. cereus strain independently from the classic B. anthracis strains and established a B. anthracis lifestyle. Therefore we suggest to designate this isolate as "B. cereus variety (var. anthracis".

  14. Adenoviral Expression of a Bispecific VHH-Based Neutralizing Agent That Targets Protective Antigen Provides Prophylactic Protection from Anthrax in Mice.

    Science.gov (United States)

    Moayeri, Mahtab; Tremblay, Jacqueline M; Debatis, Michelle; Dmitriev, Igor P; Kashentseva, Elena A; Yeh, Anthony J; Cheung, Gordon Y C; Curiel, David T; Leppla, Stephen; Shoemaker, Charles B

    2016-01-06

    Bacillus anthracis, the causative agent of anthrax, secretes three polypeptides, which form the bipartite lethal and edema toxins (LT and ET, respectively). The common component in these toxins, protective antigen (PA), is responsible for binding to cellular receptors and translocating the lethal factor (LF) and edema factor (EF) enzymatic moieties to the cytosol. Antibodies against PA protect against anthrax. We previously isolated toxin-neutralizing variable domains of camelid heavy-chain-only antibodies (VHHs) and demonstrated their in vivo efficacy. In this work, gene therapy with an adenoviral (Ad) vector (Ad/VNA2-PA) (VNA, VHH-based neutralizing agents) promoting the expression of a bispecific VHH-based neutralizing agent (VNA2-PA), consisting of two linked VHHs targeting different PA-neutralizing epitopes, was tested in two inbred mouse strains, BALB/cJ and C57BL/6J, and found to protect mice against anthrax toxin challenge and anthrax spore infection. Two weeks after a single treatment with Ad/VNA2-PA, serum VNA2-PA levels remained above 1 μg/ml, with some as high as 10 mg/ml. The levels were 10- to 100-fold higher and persisted longer in C57BL/6J than in BALB/cJ mice. Mice were challenged with a lethal dose of LT or spores at various times after Ad/VNA2-PA administration. The majority of BALB/cJ mice having serum VNA2-PA levels of >0.1 μg/ml survived LT challenge, and 9 of 10 C57BL/6J mice with serum levels of >1 μg/ml survived spore challenge. Our findings demonstrate the potential for genetic delivery of VNAs as an effective method for providing prophylactic protection from anthrax. We also extend prior findings of mouse strain-based differences in transgene expression and persistence by adenoviral vectors.

  15. [Present status of vaccines in 1989].

    Science.gov (United States)

    Roussey, M; Dabadie, A

    1989-01-01

    The authors describe 2 new vaccines now available in France: one is the GenHevac, an hepatitis B vaccine, the first virus recombinant vaccine; the other one is the Typhim Vi, a polysaccharide typhoid vaccine. Three other vaccines are currently used in foreign countries and will be soon available: the Hemophilus influenzae vaccine, the acellular pertussis vaccine and the varicella vaccine. Rotavirus and Cytomegalovirus vaccines are studied for their clinical efficacy.

  16. Flu vaccination in pregnancy

    Directory of Open Access Journals (Sweden)

    Maria Siettou

    2012-04-01

    Full Text Available In periods of seasonal influenza, during pandemic flu in the past and from recent experience that we have the emergence of influenza A (H1N1, pregnant compared with non-pregnant women are at increased risk to get sick and to develop serious complications up to mortality. Purpose: This paper examines the risks that arise for pregnant from contamination with the flu virus and the safety of influenza vaccination in pregnancy. Method: The method involves searching review and research studies in Pubmed data base mainly of the 2000 until 2009 and the words were used is pregnancy, flu vaccination, complications of the flu vaccination at the period of pregnancy. Results: Morbidity during periods of seasonal influenza in pregnant women is increased, while in times of pandemic are recorded fatalities. Based on this, specific recommendations have been made for a flu vaccination in pregnant women, both from the CDC, the American College of Obstetricians and Gynecologists in the U.S. and other official bodies like the World Health Organization, according to that the constitution of influenza vaccine in the pregnancy is necessary, given that the probability of morbidity in this period is increased at 10%. Conclusions: The studies so far to influenza vaccination in pregnancy, do not record serious complications for pregnant women and infants. However more research needs to be done on the safety of influenza vaccination in pregnancy.

  17. Alphavirus-Based Vaccines.

    Science.gov (United States)

    Lundstrom, Kenneth

    2016-01-01

    Alphavirus vectors based on Semliki Forest virus, Sindbis virus, and Venezuelan equine encephalitis virus have been widely applied for vaccine development. Naked RNA replicons, recombinant viral particles, and layered DNA vectors have been subjected to immunization in preclinical animal models with antigens for viral targets and tumor antigens. Moreover, a limited number of clinical trials have been conducted in humans. Vaccination with alphavirus vectors has demonstrated efficient immune responses and has showed protection against challenges with lethal doses of virus and tumor cells, respectively. Moreover, vaccines have been developed against alphaviruses causing epidemics such as Chikungunya virus.

  18. Research toward Malaria Vaccines

    Science.gov (United States)

    Miller, Louis H.; Howard, Russell J.; Carter, Richard; Good, Michael F.; Nussenzweig, Victor; Nussenzweig, Ruth S.

    1986-12-01

    Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

  19. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  20. Anti-addiction vaccines

    Science.gov (United States)

    Shen, Xiaoyun; Orson, Frank M.

    2011-01-01

    Despite intensive efforts to eradicate it, addiction to both legal and illicit drugs continues to be a major worldwide medical and social problem. Anti-addiction vaccines can produce the antibodies to block the effects of these drugs on the brain, and have great potential to ameliorate the morbidity and mortality associated with illicit drug intoxications. This review provides a current overview of anti-addiction vaccines that are under clinical trial and pre-clinical research evaluation. It also outlines the development challenges, ethical concerns, and likely future intervention for anti-addiction vaccines. PMID:22003367

  1. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M;

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  2. Meningococcal vaccine evolution

    Directory of Open Access Journals (Sweden)

    Gianni Bona

    2012-06-01

    Full Text Available Neisseria meningitidis is a leading cause of bacterial sepsis and meningitis worldwide. Although polysaccharide and glycoconjugate vaccines have been developed for serogroups A, C, Y and W-135, currently there are no broadly effective vaccines available for the prevention of meningococcal B disease. A general overview of the burden of the disease and the strains prevalence in the world with the focus in particular on the Italian situation is provided in this article, together with the vaccinations developed and under evaluation.

  3. 白云机场可疑炭疽事件和对航空旅行的影响%Suspicious Anthrax Events and Its Affect to the Air Travel in the Baiyuan International Airport, Guangzhou, China

    Institute of Scientific and Technical Information of China (English)

    胡龙飞

    2002-01-01

    @@ Objective: The anthrax panic first occurred in the United States in Oct., 2001 was rapidly spread worldwide within a very short period. Like other international airport in the world, there were the same suspicious events occurred in the Baiyun International Airport, Guangzhou during the period.This paper aimed to discuss the factors affecting the air travel and the effective measures to lessen the panic in the related population when this kind of suspicious anthrax event occurred.

  4. DNA vaccines and intradermal vaccination by DNA tattooing.

    Science.gov (United States)

    Oosterhuis, K; van den Berg, J H; Schumacher, T N; Haanen, J B A G

    2012-01-01

    Over the past two decades, DNA vaccination has been developed as a method for the induction of immune responses. However, in spite of high expectations based on their efficacy in preclinical models, immunogenicity of first generation DNA vaccines in clinical trials was shown to be poor, and no DNA vaccines have yet been licensed for human use. In recent years significant progress has been made in the development of second generation DNA vaccines and DNA vaccine delivery methods. Here we review the key characteristics of DNA vaccines as compared to other vaccine platforms, and recent insights into the prerequisites for induction of immune responses by DNA vaccines will be discussed. We illustrate the development of second generation DNA vaccines with the description of DNA tattooing as a novel DNA delivery method. This technique has shown great promise both in a small animal model and in non-human primates and is currently under clinical evaluation.

  5. PROGRESS ON THE ANTHRAX TOXIN AND THE CELLULAR CLONE RECEPTOR FOR ANTHRAX TOXIN%炭疽毒素及其克隆受体的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘承宜; 李艳玲; 段锐; 李燕; 蔡雄伟; 黄平

    2002-01-01

    综述炭疽毒素研究的最新进展.炭疽毒素由3种蛋白组成:致死因子(Lethal factor,LF),水肿因子(edema factor,EF)和保护性抗原(protective antigen,PA).本文主要讲述了炭疽毒素的关键致病因子--致死因子(LF)的结构和功能,炭疽毒素受体(anthrax toxin receptor,ATR)的结构及其特征性功能基团,介绍了通过基因互补对ATR进行克隆的方法,并讨论了ATR和ATR的cDNA克隆在炭疽治疗的可能应用.

  6. Vaccine safety controversies and the future of vaccination programs.

    Science.gov (United States)

    François, Guido; Duclos, Philippe; Margolis, Harold; Lavanchy, Daniel; Siegrist, Claire-Anne; Meheus, André; Lambert, Paul-Henri; Emiroğlu, Nedret; Badur, Selim; Van Damme, Pierre

    2005-11-01

    In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine "scares" continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.

  7. EXPERIMENTAL MEASLES VACCINES: A RESEARCH TOOL IN VACCINATION EVENTS

    Directory of Open Access Journals (Sweden)

    V. A. Liashenko

    2007-01-01

    Full Text Available Abstract. The review article considers different variants of measles vaccine that may be classified into two groups, i.e., vaccines that do not contain viable measles virus, and attenuated measles vaccines which could be employed in unusual manner.The first group includes DNA-vaccines, recombinant vaccine strains encoding synthesis of measles hemagglutinin and fusion protein, as well as peptide vaccines containing molecular fragments of these proteins. The mentioned variants of vaccines were effective in animal experiments, but they have not been tested in humans. The second group includes live attenuated mucosal measles vaccins applied in combination with immunomodulator(s, as aerosol and intranasally. Efficiency of these vaccines was tested and confirmed by immunization of children and adults. Mucosal measles vaccine induces local production of IgA measles antibodies, along with induced synthesis of circulating IgM and IgG antibodies against measles. The latter experimental variant could be a live attenuated measles vaccine containing some immunity-modulating agent. Elaboration of these variant was based on the known data about transient immunosuppressive activity of measles vaccine. An appropriate experimental variant represents a mixture of attenuated measles vaccine and synthetic immunomodulating agent (MP-2 peptide which protects T-lymphocytes from inhibitory effect of the measles virus. In present revue, some data are presented concerning the mechanisms of immunogenic activity and adverse effects of measles vaccines.

  8. Vaccines against typhoid fever.

    Science.gov (United States)

    Guzman, Carlos A; Borsutzky, Stefan; Griot-Wenk, Monika; Metcalfe, Ian C; Pearman, Jon; Collioud, Andre; Favre, Didier; Dietrich, Guido

    2006-05-01

    Because of high infectivity and significant disease burden, typhoid fever constitutes a major global health problem. Implementation of adequate food handling practices and establishment of safe water supplies are the cornerstone for the development of an effective prevention program. However, vaccination against typhoid fever remains an essential tool for the effective management of this disease. Currently, there are two well tolerated and effective licensed vaccines. One is based on defined subunit virulence (Vi) polysaccharide antigen and can be administered either intramuscularly or subcutaneously and the other is based on the use of live attenuated bacteria for oral administration. The advantages and disadvantages of the various approaches taken in the development of a vaccine against typhoid fever are discussed, along with the potential for future vaccine candidates.

  9. Antibacterials: A sweet vaccine

    Science.gov (United States)

    Bundle, David

    2016-03-01

    Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.

  10. Smallpox vaccine revisited.

    Science.gov (United States)

    Capriotti, Teri

    2002-12-01

    Smallpox is a serious contagious disease which is back in the public eye. Yet, most health care providers are unprepared for its return. Nurses will be key health care professionals in a smallpox outbreak or vaccination program.

  11. Veterinary vaccines against toxoplasmosis.

    Science.gov (United States)

    Hiszczyńska-Sawicka, Elżbieta; Gatkowska, Justyna M; Grzybowski, Marcin M; Długońska, Henryka

    2014-09-01

    Toxoplasma gondii is a cosmopolitan protozoan parasite that infects a wide range of mammal and bird species. Common infection leads to high economic (e.g., abortions in sheep) and human (e.g., congenital toxoplasmosis or neurotoxoplasmosis in humans) losses. With one exception (Toxovax for sheep), there are no vaccines to prevent human or animal toxoplasmosis. The paper presents the current state and challenges in the development of a vaccine against toxoplasmosis, designed for farm animals either bred for consumption or commonly kept on farms and involved in parasite transmission. So far, the trials have mostly revolved around conventional vaccines and, compared with the research using laboratory animals (mainly mice), they have not been very numerous. However, the results obtained are promising and could be a good starting point for developing an effective vaccine to prevent toxoplasmosis.

  12. Hepatitis B Vaccination Protection

    Science.gov (United States)

    Fact Sheet Hepatitis B Vaccination Protection Hepatitis B virus (HBV) is a pathogenic microorganism that can cause potentially life- threatening disease in humans. HBV infection is transmitted through exposure ...

  13. What Is a Vaccine?

    Science.gov (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  14. Tuberculosis vaccine types and timings.

    Science.gov (United States)

    Orme, Ian M

    2015-03-01

    Traditionally, the design of new vaccines directed against Mycobacterium tuberculosis, the most successful bacterial pathogen on the planet, has focused on prophylactic candidates that would be given to individuals while they are still young. It is becoming more apparent, however, that there are several types of vaccine candidates now under development that could be used under various conditions. Thus, in addition to prophylactic vaccines, such as recombinant Mycobacterium bovis BCG or BCG-boosting vaccines, other applications include vaccines that could prevent infection, vaccines that could be given in emergency situations as postexposure vaccines, vaccines that could be used to facilitate chemotherapy, and vaccines that could be used to reduce or prevent relapse and reactivation disease. These approaches are discussed here, including the type of immunity we are trying to specifically target, as well as the limitations of these approaches.

  15. Current status of rotavirus vaccines

    Institute of Scientific and Technical Information of China (English)

    Ching-Min Wang; Shou-Chien Chen; Kow-Tong Chen

    2015-01-01

    Background: Rotaviruses remain the major cause of childhood diarrheal disease worldwide and of diarrheal deaths of infants and children in developing countries. The huge burden of childhood rotavirus-related diarrhea in the world continues to drive the remarkable pace of vaccine development. Data sources: Research articles were searched using terms "rotavirus" and "rotavirus vaccine" in MEDLINE and PubMed. Articles not published in the English language, articles without abstracts, and opinion articles were excluded from the review. After preliminary screening, all articles were reviewed and synthesized to provide an overview of current vaccines and vaccination programs. Results: In this review of the global rotavirus vaccines and vaccination programs, the principles of rotavirus vaccine development and the efficacy of the currently licensed vaccines from both developed and developing countries were summarized. Conclusions: Rotavirus is a common cause of diarrhea in children in both developed and developing countries. Rotavirus vaccination is a cost-effective measure to prevent rotavirus diarrhea.

  16. Epilepsy and vaccinations: Italian guidelines.

    Science.gov (United States)

    Pruna, Dario; Balestri, Paolo; Zamponi, Nelia; Grosso, Salvatore; Gobbi, Giuseppe; Romeo, Antonino; Franzoni, Emilio; Osti, Maria; Capovilla, Giuseppe; Longhi, Riccardo; Verrotti, Alberto

    2013-10-01

    Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination.

  17. HPV vaccines: a controversial issue?

    Directory of Open Access Journals (Sweden)

    A.F. Nicol

    2016-01-01

    Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  18. 吸入性炭疽的防治措施%Imbedibility anthrax preventing and controlling measure

    Institute of Scientific and Technical Information of China (English)

    任晓波; 期滟淋

    2010-01-01

    炭疽(anthrax)是由炭疽芽胞肝菌(Bacillus anthracis)引起的人畜共患疾病.通过皮肤、呼吸道和消化道感染.吸入性炭疽即是炭疽孢子自呼吸道吸入而引起的肺炭疽,是炭疽病的一种临床类型,平时较少见,但在敌人使用生物恐怖袭击时,则是最常见最危险的疾病之一.因而,在过去、现在和未来生物恐怖袭击中,均具有重要意义[1].

  19. Prediction of protein-peptide interactions: application of the XPairIt API to anthrax lethal factor and substrates

    Science.gov (United States)

    Hurley, Margaret M.; Sellers, Michael S.

    2013-05-01

    As software and methodology develop, key aspects of molecular interactions such as detailed energetics and flexibility are continuously better represented in docking simulations. In the latest iteration of the XPairIt API and Docking Protocol, we perform a blind dock of a peptide into the cleavage site of the Anthrax lethal factor (LF) metalloprotein. Molecular structures are prepared from RCSB:1JKY and we demonstrate a reasonably accurate docked peptide through analysis of protein motion and, using NCI Plot, visualize and characterize the forces leading to binding. We compare our docked structure to the 1JKY crystal structure and the more recent 1PWV structure, and discuss both captured and overlooked interactions. Our results offer a more detailed look at secondary contact and show that both van der Waals and electrostatic interactions from peptide residues further from the enzyme's catalytic site are significant.

  20. Analysis of Anthrax Immune Globulin Intravenous with Antimicrobial Treatment in Injection Drug Users, Scotland, 2009–2010

    Science.gov (United States)

    Cui, Xizhong; Nolen, Leisha D.; Sun, Junfeng; Booth, Malcolm; Donaldson, Lindsay; Quinn, Conrad P.; Boyer, Anne E.; Hendricks, Katherine; Shadomy, Sean; Bothma, Pieter; Judd, Owen; McConnell, Paul; Bower, William A.

    2017-01-01

    We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009–2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0–5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6–11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak. PMID:27983504

  1. Eoidemic of Anthrax in Sichuan Province, 2004 -2009%2004-2009年四川省炭疽疫情分析

    Institute of Scientific and Technical Information of China (English)

    汪立茂; 李帆; 祝小平; 魏敏; 吴建林

    2011-01-01

    目的 分析四川省炭疽疫情动态及流行因素,为制定防制策略提供科学依据.方法 根据疫情资料及暴发疫情现场流调报告,对疫情资料进行病学统计分析.结果 2004 - 2009年四川省共报告炭疽病例712例,发病呈现小的上升趋势,流行表现形式以常年散发伴局部地区小暴发为主,具有一定的地域性特征,主要发病在牧区和半农半牧地区,阿坝州较高(9.33/10万)、高于甘孜州(1.96/10万)和凉山州(0.46/10万),发病季节多见于夏秋季的7~9月(55.90%),发病年龄以农牧民中的青壮年为主,男性多于女性.结论 四川省炭疽疫情呈小上升趋势,应加大健康教育力度,加强对畜间的免疫和监管,卫生、畜牧部门相互配合,及时发现和处理疫情.%Objective To analyze the epidemic situation and factors of anthrax in Sichuan province from 2004 to 2009, and provide scientific evidence for developing preventive and control strategies. Methods The data of anthrax epidemic in Sichuan province from 2004 to 2009 was analyzed by using epidemiological methods. Results There were 712 reported anthrax cases in Sichuan province from 2004 to 2009. The major epidemic form of anthrax was sporadic with outbreaks in some areas. The incidence in Aba was higher (9. 33/105) than in Ganzi (1. 96/105) and Iiangshan prefecture (0. 46/105). Anthrax was more common during June to September in summer and autumn, accounting for 55. 90% , and main in youth among peasants and stock raisers. The incidence in males was higher than that in females. Conclusion Anthrax epidemic in Sichuan province presents a minor upward trend. Health education for peasants and stock raisers, immunication and supervision among domestic animals should be strengthened. Relative departments should cooperate with each other to discover and deal with the epidemic in time.

  2. DNA vaccines against influenza.

    Science.gov (United States)

    Stachyra, Anna; Góra-Sochacka, Anna; Sirko, Agnieszka

    2014-01-01

    Genetic vaccine technology has been considerably developed within the last two decades. This cost effective and promising strategy can be applied for therapy of cancers and for curing allergy, chronic and infectious diseases, such as a seasonal and pandemic influenza. Despite numerous advantages, several limitations of this technology reduce its performance and can retard its commercial exploitation in humans and its veterinary applications. Inefficient delivery of the DNA vaccine into cells of immunized individuals results in low intracellular supply of suitable expression cassettes encoding an antigen, in its low expression level and, in turn, in reduced immune responses against the antigen. Improvement of DNA delivery into the host cells might significantly increase effectiveness of the DNA vaccine. A vast array of innovative methods and various experimental strategies have been applied in order to enhance the effectiveness of DNA vaccines. They include various strategies improving DNA delivery as well as expression and immunogenic potential of the proteins encoded by the DNA vaccines. Researchers focusing on DNA vaccines against influenza have applied many of these strategies. Recent examples of the most successful modern approaches are discussed in this review.

  3. Rationalizing vaccine injury compensation.

    Science.gov (United States)

    Mello, Michelle M

    2008-01-01

    Legislation recently adopted by the United States Congress provides producers of pandemic vaccines with near-total immunity from civil lawsuits without making individuals injured by those vaccines eligible for compensation through the Vaccine Injury Compensation Program. The unusual decision not to provide an alternative mechanism for compensation is indicative of a broader problem of inconsistency in the American approach to vaccine-injury compensation policy. Compensation policies have tended to reflect political pressures and economic considerations more than any cognizable set of principles. This article identifies a set of ethical principles bearing on the circumstances in which vaccine injuries should be compensated, both inside and outside public health emergencies. A series of possible bases for compensation rules, some grounded in utilitarianism and some nonconsequentialist, are discussed and evaluated. Principles of fairness and reasonableness are found to constitute the strongest bases. An ethically defensible compensation policy grounded in these principles would make a compensation fund available to all individuals with severe injuries and to individuals with less-severe injuries whenever the vaccination was required by law or professional duty.

  4. Recombinant baculovirus displayed vaccine

    Science.gov (United States)

    Prabakaran, Mookkan; Kwang, Jimmy

    2014-01-01

    The rapid evolution of new sublineages of H5N1 influenza in Asia poses the greatest challenge in vaccine development for pre-pandemic preparedness. To overcome the antigenic diversity of H5N1 strains, multiple vaccine strains can be designed based on the distribution of neutralizing epitopes in the globular head of H5 hemagglutinin (HA). Recently, we selected two different HAs of H5N1 strains based on the neutralizing epitopes and reactivity with different neutralizing antibodies. The HAs of selected vaccine strains were individually expressed on the baculovirus envelope (bivalent-BacHA) with its native antigenic configuration. Further, oral delivery of live bivalent-BacHA elicited broadly reactive humoral, mucosal and cell-mediated immune responses and showed complete protection against antigenically distinct H5N1 strains in mice. The strategy for the vaccine strain selection, vaccine design and route of administration will provide an idea for development of a widely protective vaccine against highly pathogenic H5N1 for pre-pandemic preparedness. PMID:23941989

  5. Vaccination strategies against influenza.

    Science.gov (United States)

    Hanon, E

    2009-01-01

    Every year, Influenza virus infection is at the origin of substantial excess in morbidity and mortality in developed as well as developing countries. Influenza viruses undergo antigenic drift which cause annual replacement of strain included in classical trivalent vaccines. Less frequently, this virus can also undergo antigenic shift, which corresponds to a major antigenic change and can lead to an extra medical burden. Several vaccines have been made available to immunize individuals against seasonal as well as pandemic influenza viruses. For seasonal Influenza vaccines, live attenuated and classical inactivated trivalent vaccines have been licensed and are widely used. Additionally, several strategies are under investigations to improve further the efficacy of existing seasonal vaccines in children and elderly. These include the use of adjuvant, increase in antigen content, or alternative route of delivery. Similarly, several approaches have been licensed to address additional challenge posed by pandemic viruses. The different vaccination strategies used to maximise protection against seasonal as well as pandemic influenza will be reviewed and discussed in the perspective the current threat posed by the H1N1v pandemic Influenza.

  6. Military Infectious Diseases Update on Vaccine Development

    Science.gov (United States)

    2011-01-24

    development thrusts • Enterotoxigenic Escherichia coli (ETEC) vaccines • Shigella vaccines • Campylobacter jejuni vaccines 2011 MHS Conference Vaccines...Injectisome extending from Shigella Injectisome Injectisome graphic 2011 MHS Conference  Campylobacter jejuni – Transmission: Foodborne – Inoculum

  7. Understanding Thimerosal, Mercury, and Vaccine Safety

    Science.gov (United States)

    ... fungus. It is used as a preservative for flu vaccines in multi-dose vials, to keep the vaccine ... as much as possible. • Today, except for some flu vaccines in multi-dose vials, no recommended childhood vaccines ...

  8. Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.

    Directory of Open Access Journals (Sweden)

    Matthew A Crawford

    Full Text Available Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms.

  9. Addressing the Federal-State-Local Interface Issues During a Catastrophic Event Such as an Anthrax Attack

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Steven L.; Lesperance, Ann M.; Upton, Jaki F.

    2010-02-01

    On October 9, 2008, federal, state and local policy makers, emergency managers, and medical and public health officials convened in Seattle, Washington, for a workshop on Addressing the Federal-State-Local Interface Issues During a Catastrophic Event Such as an Anthrax Attack. The day-long symposium was aimed at generating a dialogue about recovery and restoration through a discussion of the associated challenges that impact entire communities, including people, infrastructure, and critical systems. The Principal Federal Official (PFO) provided an overview of the role of the PFO in a catastrophic event. A high-level summary of an anthrax scenario was presented. The remainder of the day was focused on interactive discussions among federal, state and local emergency management experts in the areas of: • Decision-making, prioritization, and command and control • Public health/medical services • Community resiliency and continuity of government. Key topics and issues that resulted from discussions included: • Local representation in the Joint Field Office (JFO) • JFO transition to the Long-Term Recovery Office • Process for prioritization of needs • Process for regional coordination • Prioritization - process and federal/military intervention • Allocation of limited resources • Re-entry decision and consistency • Importance of maintaining a healthy hospital system • Need for a process to establish a consensus on when it is safe to re-enter. This needs to be across all jurisdictions including the military. • Insurance coverage for both private businesses and individuals • Interaction between the government and industry. The symposium was sponsored by the Interagency Biological Restoration Demonstration, a collaborative regional program jointly funded by the U.S. Department of Homeland Security and the U.S. Department of Defense. To aid the program’s efforts and inform the development of blueprint for recovery from a biological incident

  10. HIV Vaccination, is Breakthrough Underway?

    Science.gov (United States)

    Lu, Da-Yong; Wu, Hong-Ying; Lu, Ting-Ren; Xu, Bin; Ding, Jian

    2016-01-01

    After long defeats-almost no marked breakthrough in HIV vaccination campaign has been observed during the past two decades, and we still have not lost our faiths for the development of highly effective and low risk HIV vaccines. Many effective vaccines have been discovered and will certainly enter into the markets within the next 5 to 10 years. In order to promote HIV vaccine developments and clinical HIV therapeutic improvements, this perspective addresses the good and bad sides of currently available HIV vaccines, discusses many subjects of medical significance and finally provides up-to-date information in the field of HIV studies, in particular regarding vaccine developments and HIV pathogenesis.

  11. Increasing Childhood Influenza Vaccination

    Science.gov (United States)

    Nowalk, Mary Patricia; Lin, Chyongchiou J.; Hannibal, Kristin; Reis, Evelyn C.; Gallik, Gregory; Moehling, Krissy K.; Huang, Hsin-Hui; Allred, Norma J.; Wolfson, David H.; Zimmerman, Richard K.

    2014-01-01

    Background Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. Purpose To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. Methods In 2011–2012, 20 primary care practices treating children were randomly assigned to Intervention and Control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. Results The average vaccination differences from pre-intervention to the intervention year were significantly larger in the Intervention arm (n=10 practices) than the Control arm (n=10 practices), for children aged 2–8 years (10.2 percentage points (pct pts) Intervention vs 3.6 pct pts Control) and 9–18 years (11.1 pct pts Intervention vs 4.3 pct pts Control, p<0.05), for non-white children (16.7 pct pts Intervention vs 4.6 pct pts Control, p<0.001), and overall (9.9 pct pts Intervention vs 4.2 pct pts Control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race and intervention, the likelihood of vaccination increased with younger age group (6–23 months), white race, commercial insurance, the practice’s pre-intervention vaccination rate, and being in the Intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9–18 years. Conclusions A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza

  12. Immune Interference After Sequential Alphavirus Vaccine Vaccinations

    Science.gov (United States)

    2009-01-01

    biological weapons by adversary governments and/or terrorists [4–9]. For veterinary use, there are live, attenuated and inactivated VEE vaccines as...Alphaviruses. In: Knife DM, Howley PM, editors. Fields virology . 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. p. 1023–67. [2] Kuhn RJ...Togaviridae: the viruses and their replication. In: Knife DM, Howley PM, editors. Fields virology . 5th ed. Philadelphia, PA: Lippincott Williams

  13. Vaccine Effectiveness - How Well Does the Seasonal Flu Vaccine Work?

    Science.gov (United States)

    ... to infection with seasonal flu viruses. Information regarding vaccination history is particularly important to these types of evaluations, and can be difficult to confirm, as accurate vaccination records are not always readily available. People who ...

  14. Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development.

    Science.gov (United States)

    Giles, C; Vanniasinkam, T; Ndi, S; Barton, M D

    2015-09-01

    For decades researchers have been targeting prevention of Rhodococcus equi (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding industry has supported the ongoing efforts by researchers to develop a safe and cost effective vaccine to prevent disease in foals. Traditional vaccines including live, killed and attenuated (physical and chemical) vaccines have proved to be ineffective and more modern molecular-based vaccines including the DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate protection of foals. Newer, bacterial vector vaccines have recently shown promise for R. equi in the mouse model. This article describes the findings of key research in R. equi vaccine development and looks at alternative methods that may potentially be utilised.

  15. 9 CFR 113.318 - Pseudorabies Vaccine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Pseudorabies Vaccine. 113.318 Section... Virus Vaccines § 113.318 Pseudorabies Vaccine. Pseudorabies Vaccine shall be prepared from virus-bearing... be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from...

  16. 9 CFR 113.303 - Bluetongue Vaccine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bluetongue Vaccine. 113.303 Section... Virus Vaccines § 113.303 Bluetongue Vaccine. Bluetongue Vaccine shall be prepared from virus-bearing... be used for preparing the seeds for vaccine production. All serials of vaccine shall be prepared...

  17. Cancer Vaccines: A Brief Overview.

    Science.gov (United States)

    Thomas, Sunil; Prendergast, George C

    2016-01-01

    Vaccine approaches for cancer differ from traditional vaccine approaches for infectious disease in tending to focus on clearing active disease rather than preventing disease. In this review, we provide a brief overview of different types of vaccines and adjuvants that have been investigated for the purpose of controlling cancer burdens in patients, some of which are approved for clinical use or in late-stage clinical trials, such as the personalized dendritic cell vaccine sipuleucel-T (Provenge) and the recombinant viral prostate cancer vaccine PSA-TRICOM (Prostvac-VF). Vaccines against human viruses implicated in the development and progression of certain cancers, such as human papillomavirus in cervical cancer, are not considered here. Cancers express "altered self" antigens that tend to induce weaker responses than the "foreign" antigens expressed by infectious agents. Thus, immune stimulants and adjuvant approaches have been explored widely. Vaccine types considered include autologous patient-derived immune cell vaccines, tumor antigen-expressing recombinant virus vaccines, peptide vaccines, DNA vaccines, and heterologous whole-cell vaccines derived from established human tumor cell lines. Opportunities to develop effective cancer vaccines may benefit from seminal recent advances in understanding how immunosuppressive barricades are erected by tumors to mediate immune escape. In particular, targeted ablation of these barricades with novel agents, such as the immune checkpoint drug ipilimumab (anti-CTLA-4) approved recently for clinical use, may offer significant leverage to vaccinologists seeking to control and prevent malignancy.

  18. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future.

  19. [Results of Booster Vaccination in Children with Primary Vaccine Failure after Initial Varicella Vaccination].

    Science.gov (United States)

    Ozakiv, Takao; Nishimura, Naoko; Gotoh, Kensei; Funahashi, Keiji; Yoshii, Hironori; Okuno, Yoshinobu

    2016-05-01

    In October 2014, the varicella vaccination policy in Japan was changed from a single voluntary inoculation to two routine inoculations. This paper reports the results of booster vaccination in children who did not show seroconversion after initial vaccination (i.e., primary vaccine failure : PVF) over a 7-year period prior to the introduction of routine varicella vaccination. Between November 2007 and May 2014, 273 healthy children aged between 1.1 and 14.5 years (median : 1.7 years) underwent varicella vaccination. Before and 4 to 6 weeks after vaccination, the antibody titers were measured using an immune adherence hemagglutination (IAHA) assay and a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). In addition, side reactions were examined during the four-week period after vaccination. Children who did not show IAHA seroconversion (PVF) were recommended to receive a booster vaccination, and the measurement of antibody titers and an assessment of side reactions were performed after the booster dose. In May 2015, a questionnaire was mailed to each of the 273 participants to investigate whether they had developed varicella and/or herpes zoster after vaccination. After initial vaccination, the IAHA seroconversion rate was 75% and the mean antibody titer (Log2) with seroconversion was 4.7, while the gpELISA seroconversion rate was 84% and the mean antibody titer (Log10) with seroconversion was 2.4. Among children with PVF, 54 received booster vaccination within 81 to 714 days (median : 139 days) after the initial vaccination. After booster vaccination, the IAHA seroconversion rate was 98% and the mean antibody titer (Log2) with seroconversion was 5.8. Both the seroconversion rate and the antibody titer were higher compared with the values after the initial vaccination (p vaccination, the gpELISA seropositive rate was 100% and the mean positive antibody titer (Log 10) was 3.6 ; similar results were obtained for the IAHA assay, with a significantly higher

  20. Antiplatelet activities of anthrax lethal toxin are associated with suppressed p42/44 and p38 mitogen-activated protein kinase pathways in the platelets.

    Science.gov (United States)

    Kau, Jyh-Hwa; Sun, Der-Shan; Tsai, Wei-Jern; Shyu, Huey-Fen; Huang, Hsin-Hsien; Lin, Hung-Chi; Chang, Hsin-Hou

    2005-10-15

    Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, but the mechanism by which it induces high mortality remains unclear. We found that LT treatment could induce severe hemorrhage in mice and significantly suppress human whole-blood clotting and platelet aggregation in vitro. In addition, LT could inhibit agonist-induced platelet surface P-selectin expression, resulting in the inhibition of platelet-endothelial cell engagements. Data from Western blot analysis indicated that LT treatment resulted in the suppression of p42/44 and p38 mitogen-activated protein kinase pathways in platelets. Combined treatments with LT and antiplatelet agents such as aspirin and the RGD-containing disintegrin rhodostomin significantly increased mortality in mice. Our data suggest that platelets are a pathogenic target for anthrax LT.

  1. 75 FR 48706 - Proposed Vaccine Information Materials for Rotavirus Vaccine

    Science.gov (United States)

    2010-08-11

    ... Services (HHS). ACTION: Notice with comment period. SUMMARY: Under the National Childhood Vaccine Injury... representative in the case of a child) receiving vaccines covered under the National Vaccine Injury Compensation...-day comment period, and in consultation with the Advisory Commission on Childhood...

  2. 75 FR 48712 - Proposed Vaccine Information Materials for Influenza Vaccine

    Science.gov (United States)

    2010-08-11

    ... Services (HHS). ACTION: Notice with Comment Period. SUMMARY: Under the National Childhood Vaccine Injury... representative in the case of a child) receiving vaccines covered under the National Vaccine Injury Compensation...-day comment period, and in consultation with the Advisory Commission on Childhood...

  3. Evaluation of vaccine competition using HVT vector vaccines

    Science.gov (United States)

    Turkey herpesvirus (HVT) has been widely used as a vaccine for Marek’s disease (MD) since the 1970s. Because HVT is a safe vaccine that is poorly sensitive to interference from maternally derived antibodies, it has seen rising use as a vector for vaccines developed for protection against other comm...

  4. The Flu Vaccine and Pregnancy

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG The Flu Vaccine and Pregnancy Home For Patients Search FAQs The ... Pamphlets - Spanish FAQ189, October 2015 PDF Format The Flu Vaccine and Pregnancy Pregnancy What is influenza (the flu)? ...

  5. New Vaccines Help Protect You

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues New Vaccines Help Protect You Past Issues / Fall 2006 ... of this page please turn Javascript on. Important new vaccines have recently been approved for use and ...

  6. National Elk Refuge vaccination protocol

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Proposal by the State of Wyoming, Wyoming Game and Fish Department, to vaccinate elk on the National Elk Refuge. The proposal provides a protocol for vaccinating elk...

  7. PREDICTION OF AEROSOL HAZARDS ARISING FROM THE OPENING OF AN ANTHRAX-TAINTED LETTER IN AN OPEN OFFICE ENVIRONMENT USING COMPUTATIONAL FLUID DYNAMICS

    Directory of Open Access Journals (Sweden)

    FUE-SANG LIEN

    2010-09-01

    Full Text Available Early experimental work, conducted at Defence R&D Canada–Suffield, measured and characterized the personal and environmental contamination associated with simulated anthrax-tainted letters under a number of different scenarios in order to obtain a better understanding of the physical and biological processes for detecting, assessing, and formulating potential mitigation strategies for managing the risks associated with opening an anthrax-tainted letter. These experimental investigations have been extended in the present study to simulate numerically the contamination from the opening of anthrax-tainted letters in an open office environment using computational fluid dynamics (CFD. A quantity of 0.1 g of Bacillus atropheus (formerly referred to as Bacillus subtilis var globigii (BG spores in dry powder form, which was used here as a surrogate species for Bacillus anthracis (anthrax, was released from an opened letter in the experiment. The accuracy of the model for prediction of the spatial distribution of BG spores in the office from the opened letter is assessed qualitatively (and to the extent possible, quantitatively by detailed comparison with measured BG concentrations obtained under a number of different scenarios, some involving people moving within the office. The observed discrepancy between the numerical predictions and experimental measurements of concentration was probably the result of a number of physical processes which were not accounted for in the numerical simulation. These include air flow leakage from cracks and crevices of the building shell; the dispersion of BG spores in the Heating, Ventilation, and Air Conditioning (HVAC system; and, the effect of deposition and re-suspension of BG spores from various surfaces in the office environment.

  8. Analysing the spatial patterns of livestock anthrax in Kazakhstan in relation to environmental factors: a comparison of local (Gi*) and morphology cluster statistics.

    Science.gov (United States)

    Kracalik, Ian T; Blackburn, Jason K; Lukhnova, Larisa; Pazilov, Yerlan; Hugh-Jones, Martin E; Aikimbayev, Alim

    2012-11-01

    We compared a local clustering and a cluster morphology statistic using anthrax outbreaks in large (cattle) and small (sheep and goats) domestic ruminants across Kazakhstan. The Getis-Ord (Gi*) statistic and a multidirectional optimal ecotope algorithm (AMOEBA) were compared using 1st, 2nd and 3rd order Rook contiguity matrices. Multivariate statistical tests were used to evaluate the environmental signatures between clusters and non-clusters from the AMOEBA and Gi* tests. A logistic regression was used to define a risk surface for anthrax outbreaks and to compare agreement between clustering methodologies. Tests revealed differences in the spatial distribution of clusters as well as the total number of clusters in large ruminants for AMOEBA (n = 149) and for small ruminants (n = 9). In contrast, Gi* revealed fewer large ruminant clusters (n = 122) and more small ruminant clusters (n = 61). Significant environmental differences were found between groups using the Kruskall-Wallis and Mann-Whitney U tests. Logistic regression was used to model the presence/absence of anthrax outbreaks and define a risk surface for large ruminants to compare with cluster analyses. The model predicted 32.2% of the landscape as high risk. Approximately 75% of AMOEBA clusters corresponded to predicted high risk, compared with ~64% of Gi* clusters. In general, AMOEBA predicted more irregularly shaped clusters of outbreaks in both livestock groups, while Gi* tended to predict larger, circular clusters. Here we provide an evaluation of both tests and a discussion of the use of each to detect environmental conditions associated with anthrax outbreak clusters in domestic livestock. These findings illustrate important differences in spatial statistical methods for defining local clusters and highlight the importance of selecting appropriate levels of data aggregation.

  9. Analysing the spatial patterns of livestock anthrax in Kazakhstan in relation to environmental factors: a comparison of local (Gi* and morphology cluster statistics

    Directory of Open Access Journals (Sweden)

    Ian T. Kracalik

    2012-11-01

    Full Text Available We compared a local clustering and a cluster morphology statistic using anthrax outbreaks in large (cattle and small (sheep and goats domestic ruminants across Kazakhstan. The Getis-Ord (Gi* statistic and a multidirectional optimal ecotope algorithm (AMOEBA were compared using 1st, 2nd and 3rd order Rook contiguity matrices. Multivariate statistical tests were used to evaluate the environmental signatures between clusters and non-clusters from the AMOEBA and Gi* tests. A logistic regression was used to define a risk surface for anthrax outbreaks and to compare agreement between clustering methodologies. Tests revealed differences in the spatial distribution of clusters as well as the total number of clusters in large ruminants for AMOEBA (n = 149 and for small ruminants (n = 9. In contrast, Gi* revealed fewer large ruminant clusters (n = 122 and more small ruminant clusters (n = 61. Significant environmental differences were found between groups using the Kruskall-Wallis and Mann- Whitney U tests. Logistic regression was used to model the presence/absence of anthrax outbreaks and define a risk surface for large ruminants to compare with cluster analyses. The model predicted 32.2% of the landscape as high risk. Approximately 75% of AMOEBA clusters corresponded to predicted high risk, compared with ~64% of Gi* clusters. In general, AMOEBA predicted more irregularly shaped clusters of outbreaks in both livestock groups, while Gi* tended to predict larger, circular clusters. Here we provide an evaluation of both tests and a discussion of the use of each to detect environmental conditions associated with anthrax outbreak clusters in domestic livestock. These findings illustrate important differences in spatial statistical methods for defining local clusters and highlight the importance of selecting appropriate levels of data aggregation.

  10. Vaccines for the elderly.

    Science.gov (United States)

    Del Giudice, Giuseppe; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix

    2015-01-01

    The aging of the human population is posing serious challenges to research and to public health authorities in order to prevent diseases that more frequently affect the elderly, a portion of the population that will increase more and more in the coming years. While some vaccines exist and are used in the elderly to effectively fight against some infections (e.g. influenza, pneumococci, varicella-zoster virus, diphtheria, and tetanus), still a lot of work remains to be done to better adapt these vaccines and to develop new ones for this age group. The prevention of infectious diseases affecting the elderly can be successful only through a holistic approach. This approach will aim at the following: (1) a deeper understanding of the mechanisms leading to the senescence of the immune system, (2) a better and broader use of vaccines recommended for the elderly, (3) the use of vaccines currently considered only for other age groups and (4) actively priming the population when they are immunological competent, before the physiological waning of immune responsiveness may affect the beneficial effects of vaccination.

  11. Vaccination against seasonal influenza

    CERN Multimedia

    GS Department

    2010-01-01

    This year, as usual, the Medical Service is helping to promote vaccination against seasonal influenza. Vaccination against seasonal flu is especially recommended for anyone who suffers from chronic pulmonary, cardio-vascular or kidney disease or diabetes, is recovering from a serious illness or major surgery, or is over 65 years of age. The flu virus is transmitted through the air and through contact with contaminated surfaces, so frequent hand-washing with soap and/or an antiseptic hand wash is of great importance. As soon as the first symptoms appear (fever above 38°, shivering, coughing, muscle and/or joint pains, generalised weakness), you are strongly recommended to stay at home to avoid spreading the virus. Anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor), with their dose of vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement through UNIQA...

  12. Economics of vaccines revisited.

    Science.gov (United States)

    Postma, Maarten J; Standaert, Baudouin A

    2013-05-01

    Performing a total health economic analysis of a vaccine newly introduced into the market today is a challenge when using the conventional cost-effectiveness analysis we normally apply on pharmaceutical products. There are many reasons for that, such as: the uncertainty in the total benefit (direct and indirect) to be measured in a population when using a cohort model; (1) appropriate rules about discounting the long-term impact of vaccines are absent jeopardizing therefore their value at the initial investment; (2) the presence of opposite contexts when introducing the vaccine in developed vs. the developing world with high benefits, low initial health care investment for the latter vs. marginal benefit and high cost for the former; with a corresponding paradox for the vaccine becoming very cost-effective in low income countries but rather medium in middle low to high middle income countries; (3) and the type of trial assessment for the newer vaccines is now often performed with immunogenicity reaction instead of clinical endpoints which still leaves questions on their real impact and their head-to-head comparison. (4.)

  13. 炭疽毒素及其致病机制的研究进展%Progress in research on anthrax toxins and their pathogenesis

    Institute of Scientific and Technical Information of China (English)

    武利涛; 魏建春; 海荣

    2012-01-01

    Anthrax toxins include edema toxin (ET) and lethal toxin (LT) which are critical pathogenic factors produced by Bacillus anthracis. ET is composed of protective antigen (PA) and edema factor (EF) , while a mixture of PA and lethal factor (LF) form LT. This review summaries the progress in research on anthrax toxins and their pathogenesis from the aspects of the gene, structure and biological activity and the scientific significance of the research in the prevention and control of anthrax.%炭疽毒素包括水肿毒素( edema toxin,ET)和致死毒素(lethal toxin,LT),是炭疽芽胞杆菌产生的重要致病因子.ET由保护性抗原(protective antigen,PA)和水肿因子(edema factor,EF)组成,LT由PA和致死因子(lethal factor,LF)组成.本文从基因、结构及生物学活性等方面概述了炭疽毒素各组分在炭疽芽胞杆菌致病机制中的作用方式,并阐述了其对炭疽防治措施的科学指导意义.

  14. Clinical features and nursing of cutaneous anthrax patients%皮肤炭疽患者的临床特征与护理

    Institute of Scientific and Technical Information of China (English)

    阴嘉微

    2014-01-01

    Objective To explore proper nursing interventions for cutaneous anthrax patients. Methods According to clinic features of the patients with cutaneous anthrax, sterilized insulation, individual protection, proper disposal of patients’wounded part, excreta and applications, as well as mental counseling and health education, were used to observe whether these interventions could enhance patients’recovery and prevent hospital infection. Results By using the above-mentioned methods all 13 cutaneous anthrax patients recovered quickly and no hospital infection incidents took place. Conclusion Proper nursing interventions can prevent hospital infection and promote recovery.%目的:探索适合皮肤炭疽患者的护理措施。方法针对皮肤炭疽的临床特点,应用消毒隔离、个人防护,对患者患处、排泄物和应用物处理,并经心理疏导、健康教育,观察是否可促进患者康复及杜绝医院内感染。结果13例皮肤炭疽患者经上述处理后未发生院内交叉感染,全部痊愈出院。结论适宜的护理措施可防止皮肤炭疽患者医院内感染,促进疾病的康复。

  15. A brief history of vaccines & vaccination in India.

    Science.gov (United States)

    Lahariya, Chandrakant

    2014-04-01

    The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

  16. A brief history of vaccines & vaccination in India

    Directory of Open Access Journals (Sweden)

    Chandrakant Lahariya

    2014-01-01

    Full Text Available The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI (1978 and then Universal Immunization Programme (UIP (1985 were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

  17. Clinical Impact of Vaccine Development.

    Science.gov (United States)

    Nambiar, Puja H; Daza, Alejandro Delgado; Livornese, Lawrence L

    2016-01-01

    The discovery and development of immunization has been a singular improvement in the health of mankind. This chapter reviews currently available vaccines, their historical development, and impact on public health. Specific mention is made in regard to the challenges and pursuit of a vaccine for the human immunodeficiency virus as well as the unfounded link between autism and measles vaccination.

  18. Current scenario of malaria vaccine

    Directory of Open Access Journals (Sweden)

    Jarnail Singh Braich

    2012-04-01

    Full Text Available Malaria is one of the deadliest infectious diseases that affects millions of people worldwide including India. As an addition to chemoprophylaxis and other antimalarial interventions malaria vaccine is under extensive research since decades. The vaccine development is more difficult to predict than drug development and presents a unique challenge as already there has been no vaccine effective against a parasite. Effective malaria vaccine could help eliminate and eradicate malaria; there are currently 63 vaccine candidates, 41 in preclinical and clinical stages of development. Vaccines are being designed to target pre-erythrocytic stages, erythrocytic stage or the sexual stages of Plasmodium taken up by a feeding mosquito, or the multiple stages. Two vaccines in preclinical and clinical development target P. falciparum; and the most advanced candidate is the pre-erythrocytic vaccine RTS,S which is in phase-III clinical trials. It is likely that world's first malaria vaccine will be available by 2015 at the country level. More efficacious second generation malaria vaccines are on the way to development. Safety, efficacy, cost and provision of the vaccine to all communities are major concerns in malaria vaccine issue. [Int J Basic Clin Pharmacol 2012; 1(2.000: 60-66

  19. Needle-free influenza vaccination

    NARCIS (Netherlands)

    Amorij, Jean-Pierre; Hinrichs, Wouter L.J.; Frijlink, Henderik W.; Wilschut, Jan C.; Huckriede, Anke

    2010-01-01

    Vaccination is the cornerstone of influenza control in epidemic and pandemic situations. Influenza vaccines are typically given by intramuscular injection. However, needle-free vaccinations could offer several distinct advantages over intramuscular injections: they are pain-free, easier to distribut

  20. [About of vaccination].

    Science.gov (United States)

    Di Pietro, Maria Luisa; Refolo, Pietro; González-Melado, Fermín J

    2012-01-01

    The debate over compulsory or merely recommended vaccination remains open, albeit latent, in those countries that have mandatory vaccine schedules. Despite the advantages of preventive immunization from the point of medical, economic and social features, it's clear, in the current status of medical ethics, that the exercise of patient autonomy calls for personal responsibility in the election of treatments and, in fact, the vaccines. Therefore, it is necessary to change the simple idea of prevention as , characteristic of a in order to pass to a preventative medicine concept that will be able to support the achievement of moral attitudes towards achieving the good for the individual and for the community. This is only possible from a wherever is possible to present an alternative between mandatory vs. recommendation from the concept of that, with the help of a series of measures, could combine the effective protection for the whole community with the responsible exercise of the personal autonomy.