Influence of sodium glutamate, bubbling N2-gas and superficial aeration on tetanus toxin production in Clostridium tetani cultures (original) (raw)
Related papers
The Lancet, 2007
Maternal and neonatal tetanus are important causes of maternal and neonatal mortality, claiming about 180 000 lives worldwide every year, almost exclusively in developing countries. Although easily prevented by maternal immunisation with tetanus toxoid vaccine, and aseptic obstetric and postnatal umbilical-cord care practices, maternal and neonatal tetanus persist as public-health problems in 48 countries, mainly in Asia and Africa. Survival of tetanus patients has improved substantially for those treated in hospitals with modern intensive-care facilities; however, such facilities are often unavailable where the tetanus burden is highest. The Maternal and Neonatal Tetanus Elimination Initiative assists countries in which maternal and neonatal tetanus has not been eliminated to provide immunisation with tetanus toxoid to women of childbearing age. The ultimate goal of this initiative is the worldwide elimination of maternal and neonatal tetanus. Since tetanus spores cannot be removed from the environment, sustaining elimination will require improvements to presently inadequate immunisation and health-service infrastructures, and universal access to those services. The renewed worldwide commitment to the reduction of maternal and child mortality, if translated into eff ective action, could help to provide the systemic changes needed for long-term elimination of maternal and neonatal tetanus.
Infecção por Clostridium tetani no recém-nascido: revisão sobre o tétano neonatorum
Revista Brasileira de Terapia Intensiva, 2011
Although tetanus is a preventable disease by vaccination, it continues to claim lives around the world. Whereas cases of accidental origin reflect insufficient population immunization, tetanus neonatorum reveals a doublenature fault-poor vaccination coverage of adults coupled with difficulties accessing appropriate prenatal care; this situation is aggravated by the extreme severity of tetanus in this age group in which the mortality rate can reach up to 80%. The early detection of tetanus in neonates is essential for immediately initiating the proper therapy. Therefore, although reaching an early diagnosis of tetanus is important, the most relevant aspect is related to the appropriate management and prophylaxis of this disease. Consequently, the aim of this article is to review neonatorum tetanus with an emphasis on its therapy and prevention.
Preparative Biochemistry and Biotechnology, 2018
Chemically inactivated tetanus toxin (tetanus toxoid, TT), purified from cultures of a virulent Clostridium tetani strain, is the active pharmaceutical ingredient of anti-tetanus vaccines. Culture clarification for TT production and is usually performed by filtration-based techniques. Final clarification of the culture supernatant is achieved by passage through 0.2 mm pore size filtering membranes. Large particles removal (primary clarification) before final filtration (secondary clarification) reduces costs of the overall clarification process. With this aim, chitosan-induced particle aggregation was assessed as an alternative for primary clarification. Three chitosan variants were tested with similar results. Optimal clarification of culture supernatant was achieved by the addition of 8 mg chitosan per l of culture. Extrapolation analysis of filter sizing results indicate that 100 l of chitosan-treated supernatant can be finally filtered with a 0.6 m2 normal filtration cartridge of 0.45 þ 0.2 mm pore size. The clarified material is compatible with current standard downstream processing techniques for TT purification. Thus, chitosan-induced particle aggregation is a suitable operation for primary clarification.
Effect of Medium Composition on the Production of Tetanus Toxin by Clostridium tetani
Biotechnology Progress, 2008
The tetanus toxin is a neurotoxin synthesized by the bacillus Clostridium tetani that, after detoxification with formaldehyde, still exhibits antigenic and immunologic properties, hence its denomination of tetanus toxoid. Such a neurotoxin is produced by cultivation of the microorganism in vegetative form on a relatively complex specific medium containing glucose and peptone. The simultaneous effects of the starting levels of glucose (G 0 ) and N-Z Case TT (NZ 0 ) as carbon and nitrogen sources, respectively, on the production of tetanus toxin have been investigated in this work in static cultivations by means of a five-level star-shaped experimental design and evaluated by response surface methodology (RSM) for optimization purposes. The highest final average yield of tetanus toxin (72 L f /mL), achieved at G 0 ) 9.7 g/L and NZ 0 ) 43.5 g/L, was 80% higher than that obtained with standard cultivations (G 0 ) 8.0 g/L and NZ 0 ) 25.0 g/L).
Performance and potency of tetanus toxoid: Implications for eliminating neonatal tetanus
Bulletin of the World Health Organisation
Neonatal tetanus (NT) is a major cause of mortality in developing countries, with over 400000 deaths estimated to occur annually. WHO has adopted the goal of eliminating NT worldwide, and a major strategy for its prevention is the administration of at least two properly spaced doses of tetanus toxoid (TT) to women of childbearing age in high-risk areas to protect passively their newborns at birth. In certain countries the locally produced TT vaccine has been shown to be subpotent, while other countries have reported NT among infants born to vaccinated women.
Biotechnology and Bioprocess Engineering, 2016
Clostridium tetani, a spore-forming anaerobic bacterium, and a casein-based semisynthetic medium were used to produce tetanus toxin in this study. N-Z-Case TT (casein hydrolysate) solution and glucose stock media were mixed and autoclaved, which resulted in tetanus toxin expression. The toxin was expressed when the N-Z-Case TT solution reacted with the glucose stock at a high temperature, creating an adequate amount of Maillard reaction products (MRPs). After accumulating in C. tetani cells, tetanus toxin was secreted into the medium when cell lysis was induced by surface aeration. C. tetani was cultivated and tetanus toxin was expressed in a single-use bioreactor, which produced 80 Lf/mL of tetanus toxin in a medium with MRPs. While using the correct medium to induce tetanus toxin was important, other factors played a part in achieving the desired concentration of the toxin, including the medium processing and culture methods inside the bioreactor. Tetanus toxoid with a purity level greater than 2,500 Lf/mgPN was obtained by detoxifying and purifying the toxin recovered from the fermenter or single-use bioreactor. A single-use bioreactor could be used in a limited space without the need for constructing a large scale production facility, to produce the tetanus toxoid antigen for clinical trials.
Clostridium tetani bacteraemia
Journal of Medical Microbiology, 2012
Tetanus is a life-threatening but preventable disease caused by the toxin of Clostridium tetani, a ubiquitous, spore-forming, gram-positive bacillus found in high concentrations in soil and animal excrement. Reported tetanus cases have declined >95%, and deaths from tetanus have declined >99% in the United States since 1947, when the disease became reportable nationally. To update a previous report (1) and to determine the populations at greatest risk for the disease, CDC analyzed cases reported to the National Notifiable Diseases Surveillance System (NNDSS) during 2001-2008. This report summarizes the results of that analysis, which found that 233 tetanus cases were reported during 2001-2008; among the 197 cases with known outcomes, the case-fatality rate was 13.2%. Average annual incidence during that period was 0.10 per 1 million population overall and 0.23 among persons aged ≥65 years. Incidence among Hispanics was nearly twice that among non-Hispanics, a difference accounted for by 16 cases among Hispanic injection drug users (IDUs). Among the 92 patients for whom tetanus toxoid-containing (TT) vaccination status was available, 37 (40.2%) had received no doses of TT vaccine. Thirty (15.4%) of 195 patients had diabetes, and 27 (15.3%) of 176 were IDUs. Of 51 patients with an acute wound and a surveillance report complete enough to evaluate tetanus prophylaxis, 49 (96.1%) had not received appropriate prophylaxis. Tetanus remains a rare but life-threatening disease in the United States. Health-care providers should ensure up-to-date TT vaccination of all their patients, especially persons aged ≥65 years, persons with diabetes, and injection drug users. From 1947 to 2008, the number of tetanus cases reported each year, which already had decreased greatly since 1900, continued to decline (Figure), in part because of continued use of tetanus antitoxin for wound management and introduction of TT vaccines in the 1930s and 1940s, which led to universal childhood immunization and the addition of decennial TT boosters for adults (2,3). A major contributor to the decline in morbidity was the near elimination of neonatal tetanus, a result attributable to improved childbirth practices and to
More than a Toxin: Protein Inventory of Clostridium tetani Toxoid Vaccines
Proteomes
Clostridium tetani is the etiological agent of tetanus, a life-threatening bacterial infection. The most efficient protection strategy against tetanus is a vaccination with the C. tetani neurotoxin, which is inactivated by formaldehyde-crosslinking. Since we assumed that besides the tetanus toxin, other proteins of C. tetani may also be present in toxoid preparations, we analyzed commercially available vaccines from different countries in respect to their protein content using mass spectrometry. In total 991 proteins could be identified in all five analyzed vaccines, 206 proteins were common in all analyzed vaccines and 54 proteins from the 206 proteins were potential antigens. The additionally present proteins may contribute at least partially to protection against C. tetani infection by supporting the function of the vaccine against the devastating effects of the tetanus toxin indirectly. Two different label-free protein quantification methods were applied for an estimation of pro...
Tetanus – A Review Of Current Concepts In Management
Benin Journal of Postgraduate Medicine, 2009
Tetanus is a vaccinepreventable disease that yearly causes a total of 309,000 deaths. Reports showed up to 1 million cases annually, mostly in underdeveloped countries. Clostridium tetani, the causative organism, is widespread in the faeces of domestic animals and humans, while spores of C. tetani are abundant in soil and in the environment surrounding the habitation of humans and animals. In developing countries, mortality rates are as high as 28 per 100,000; in North America the rate is less than 0.1 per 100,000. Immunization programs clearly decreased neonatal tetanus deaths, and some recent evidence suggests progress in prevention throughout the World. Tetanus remains a great public health problem in developing countries such as Nigeria and it is associated with high mortality, but the understanding of the epidemiological aspects of this disease forms the basis of preventive strategies in any community. This paper reviewed the history, epidemiology and clinical diagnosis of tetanus and emphasized the current opinions in the management of tetanus outlining the various suggested treatment plans from experts in developing countries which form the basis for World Health Organization recommendations.