Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
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Vaccines comprising combinations of diphtheria, tetanus and pertussis (DTP) components with Haemophilus influenzae b polysaccharide--protein conjugates (DTP-Hib) are now available. Combinations of DTP-Hib with additional components such as inactivated poliomyelitis vaccine, hepatitis B vaccine, meningococcal and pneumococcal polysaccharide-protein conjugates are under development. Other combinations, such as Hib vaccine with meningococcal A, B and C components and possibly pneumococcal conjugates, or non-capsulated Haemophilus components combined with pneumococcal conjugates, developed against bacterial meningitis and otitis media respectively, are of potential interest. Combination vaccines against enteric infections and including potentially cholera, typhoid, ETEC, Shigella, rotavirus and possibly Campylobacter and Helicobacter components, may become available in the longer term. The control of these combinations is likely to be based on pharmacopoeial requirements for the individual components. However, the evaluation of combinations may not be straightforward and the interaction of the components with each other may influence reactogenicity, immunogenicity and stability and will complicate laboratory control tests. Indications of this have already arisen with some DTP-Hib combinations but are likely to increase as additional components are added. For example, the use of diphtheria and tetanus proteins as carriers for multiple polysaccharide conjugates may lead to excessive antitoxin production and epitope suppression of anti-polysaccharide responses. Other problems may result from competition for binding sites on adjuvant molecules. The requirements for new vaccine combinations need to be considered carefully and should not be made solely on assumptions based on the properties of individual components.
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PMID:Control testing of combined vaccines: a consideration of potential problems and approaches. 777 62

The potency tests for bacterial vaccines are quite diverse. For some products (pertussis, cholera, anthrax, typhoid and BCG vaccines) these are specified as Additional Standards in the Code of Federal Regulations. For other products (tetanus and diphtheria toxoids, plague vaccine) the testing is done according to so-called Minimum Requirements, which have less regulatory authority than Additional Standards. Still other products (e.g., polysaccharide conjugate vaccines, acellular pertussis vaccine, live oral typhoid) are tested according to individualized criteria that are contained in their specific Product License Applications. For some products there is inadequate knowledge of the pathogenic mechanisms and/or protective factors to design valid in vitro potency tests. In these cases, animal testing with subsequent serologic evaluation or challenge testing is often necessary. Examples would include vaccines such as cholera and plague vaccines. The FDA supports the elimination of animal testing when suitable alternatives are available. Thus, many of the potency tests, especially for newer products, rely on in vitro characterization. For example, the immunogenicity of conventional polysaccharide vaccines is largely proportional to their molecular weight. Potency testing therefore relies heavily on physical characterization in terms of composition, molecular weight, and quantity.
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PMID:Potency testing of bacterial vaccines for human use. 811 90

Stability problems in relation to bacterial vaccines vary widely between different types of product. Killed whole cell bacterial vaccines including pertussis, cholera and typhoid vaccines generally show a high degree of stability of potency. Reversion to toxicity may occur in incompletely inactivated pertussis vaccines. Live attenuated vaccines such as BCG and Ty21a typhoid vaccines lose potency through loss of viability when exposed to adverse conditions. Both vaccines are susceptible to ultra violet radiation but Ty21a also has low thermal stability. Its fragility is probably a consequence of multiple mutations affecting structural and metabolic factors. Diphtheria and tetanus toxoids generally show high stability of potency. Reversion to toxicity may occur if the toxoiding process is inadequate. Decline in potency may result from exposure to adverse conditions, such as freezing, that affect the interaction with the adjuvant. Similar problems may be encountered with purified subunit vaccines such as acellular pertussis preparations. Some components, in particular pertussis toxin and filamentous haemagglutinin, show inherent low stability and degrade on storage at refrigerator temperatures unless stabilized by a protein cross-linking agent. Bacterial proteases carried over from the cell cultures may also be responsible for degradation of purified components. Purified bacterial polysaccharides usually show high stability if freeze-dried under appropriate conditions. Catalytic degradation may occur however, if the stabilizers are of inadequate purity. Polysaccharide-protein conjugates such as Haemophilus influenzae b (Hib) polyribosylribityl phosphate-protein conjugates show high thermal stability if freeze dried. In the liquid state, such conjugates tend to degrade by hydrolysis of the polysaccharide chains. Combined vaccines may present special stability problems because of the interaction of the various components in the liquid state. It can be difficult to freeze-dry some components of such vaccines, particularly aluminium hydroxide-adsorbed diphtheria-tetanus-pertussis (DTP) components. Slow release vaccines based on polyglycolide-factolide microspheres may show suboptimal stability of encapsulated antigen under both in vitro conditions as a result of gradual acidification through polymer hydrolysis. Vaccines based on the use of live recombinant strains to express heterologous protective antigens may present special stability problems. Apart from the carrier strains, heterologous genes carried on plasmids may be subject to spontaneous deletion under adverse conditions. These issues have received relatively little attention hitherto but are likely to achieve greater prominence as development of such preparations proceeds.
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PMID:Reasons for instability of bacterial vaccines. 885 8

The current status and future prospects of vaccines for adults are discussed. For every child in America who dies of a vaccine-preventable disease, about 400 adults die of such a disease. Evidence of the merit of influenza vaccination continues to accumulate, yet < 30% of high-risk people younger than 65 have been vaccinated. Use of pneumococcal vaccine lags behind that of influenza vaccine. Serious discrepancies in immunization levels exist among different segments of U.S. adult society. A vaccination status assessment is now recommended for everyone reaching the age of 50. New vaccines are available to prevent varicella, hepatitis A, and typhoid fever. There are now two formulations of hepatitis A virus vaccine; adult users of these vaccines include travelers, people relocating to areas with poor sanitation, military personnel, laboratory workers, and hemophiliacs. New rabies vaccines may be the next vaccines to be used primarily in adults. Vaccines against pertussis, Lyme disease, cholera, herpes simplex, malaria, other infectious diseases, and cancer are in various stages of development. For health care personnel in areas where there is a strong likelihood of Mycobacterium tuberculosis transmission and infection, BCG vaccination is recommended. The risk of immunization to a person infected with the human immunodeficiency virus is likely outweighed by the protection offered against other health threats. Health systems should select tetanus-diphtheria toxoids adsorbed for their formularies for immunizing adults, not monovalent tetanus toxoid. Vaccines are available to prevent a growing list of infectious diseases but are underused in adults.
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PMID:Status and future of vaccines for adults. 904 59

A new needleless jet-injector, Mini-Imojet, was developed that administers liquid vaccines from a single-use, pre-filled cartridge named Imule, which avoids the risk of cross-contamination. We conducted clinical trials in several settings in France and West Africa to compare the immunogenicity and tolerance of five vaccines (influenza vaccine, Vi capsular polysaccharide typhoid vaccine, tetanus toxoid vaccine, diphtheria-tetanus-whole cell pertussis vaccine, and inactivated hepatitis A vaccine) administered with the Imule system vs standard syringe technique. In each vaccine study, all subjects of either group were tested for serum antibody titres to calculate the geometrical mean titres and seroconversion rates after complete vaccination. Immediate local-reactions were noted after each injection, and local and general reactions were evaluated during a predetermined period of follow-up. When delivered by the Imule technique, all the administered vaccines were of equivalent or superior immunogenicity, compared to the syringe technique. The tolerance to vaccines injected by the Imule system was acceptable in all studies. The most frequently observed reactions were mild (e.g. minor bleeding, superficial papules, erythema and induration) and could be considered to be inherent to the injection technique. The technical and safety advantages of the Mini-Imojet/Imule system, compared to sterilizable, standard disposable or autodestruct syringes and to classical multi-dose vial jet-injectors, reinforces the interest of this new injection technique for collective immunizations.
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PMID:Clinical immunogenicity and tolerance studies of liquid vaccines delivered by jet-injector and a new single-use cartridge (Imule): comparison with standard syringe injection. Imule Investigators Group. 914 Dec 17

Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophilus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti-inflammatory experimental vaccines against multiple sclerosis and insulin-dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these efficiently in plants. These recombinant antibodies are opening out an era of highly specific and safe therapeutic interventions. Human recombinant antibodies would be invaluable for treating patients with terminal tetanus and rabies. Antibodies are already in use for treatment of cancer, rheumatoid arthritis and allergies. An advantage of preformed antibodies directed at a defined target and given in adequate amounts is the certainty of efficacy in every recipient, in contrast to vaccines, where the quality and quantum of immune response varies from individual to individual.
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PMID:The impact of new technologies on vaccines. 1073 30

The 20th century has witnessed many important events in the control of infectious diseases that mostly affect children. In addition to the eradication of smallpox, the interruption of poliomyelitis transmission in many countries with a distinct possibility of its eradication by the turn of this century are some of the major achievements. Also, the rates of other vaccine preventable diseases such as measles, pertussis and diphtheria have gone down significantly. The discovery and use of vaccines have made it possible to save approximately 8 million deaths, annually. This is in addition to the reduction in millions of children's suffering and disability. It is now important to build on these gains through adequate utilisation of other vaccines e.g., hepatitis B, typhoid and Haemophilus influenzae type b that are currently available, but in limited use. But, a high level of coverage for any vaccination programme is a pre-requisite to witness the effective reduction of the specific disease against which child population is vaccinated. This paper reviews the coverage levels by surveys in the last 3 years. It has been observed that vaccination coverage levels are falling. Keeping the promises of immunising every child to fulfill his/her right is the need of the hour. To achieve this the major action points are: (a) The need for organising fixed immunisation sessions at the community, where low proportion of sessions are held; and (b) The need to improve demand generation activities where the coverage is poor despite better service availability at the community level. Therefore, the challenge for the next century is to make sure that the enormous impact of vaccines on the health and well-being of the population is maintained as well as expanded. Vaccines that effectively prevent rotavirus diarrhoea, pneumococcal pneumonia, menigococcal meningitis, if made available, could prevent deaths up to two million a year. Research efforts are currently under progress to develop new vaccines against malaria, tuberculosis, shigella-induced dysentery, and Esch coli-induced diarrhoea.
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PMID:Trends and determinants of immunisation coverage in India. 1101 38

Adult immunization is a neglected and underpublicised issue in Southeast Asia. Vaccine-preventable diseases cause unnecessary morbidity and mortality among adults in the region, while inadequate immunization results in unnecessary costs, including those associated with hospitalization, treatment, and loss of income. Childhood vaccination coverage is high for the EPI diseases of diphtheria, tetanus and pertussis; however, unvaccinated, undervaccinated, and aging adults with waning immunity remain at risk from infection and may benefit from vaccination. Catch-up immunization is advisable for adults seronegative for hepatitis B virus, while immunization against the hepatitis A and varicella viruses may benefit those who remain susceptible. Among older adults, immunization against influenza and pneumococcal infections is likely to be beneficial in reducing morbidity and mortality. Certain vaccinations are also recommended for specific groups, such as rubella for women of child-bearing age, typhoid for those travelling to high-endemicity areas, and several vaccines for high-risk occupational groups such as health care workers. This paper presents an overview of a number of vaccine-preventable diseases which occur in adults, and highlights the importance of immunization to protect those at risk of infection.
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PMID:Adult immunization--a neglected issue in Southeast Asia. 1102 89

The Centers for Disease Control and Prevention has identified immunization as the most important public health advance of the 20th century. The purpose of this article is to review the changes that have taken place in active immunization in the United States over the past decade. Since 1990, new vaccines have become available to prevent five infectious diseases: varicella, rotavirus, hepatitis A, Lyme disease, and Japanese encephalitis virus infection. Improved vaccines have been developed to prevent Haemophilus influenzae type b, pneumococcus, pertussis, rabies, and typhoid infections. Immunization strategies for the prevention of hepatitis B, measles, meningococcal infections, and poliomyelitis have changed as a result of the changing epidemiology of these diseases. Combination vaccines are being developed to facilitate the delivery of multiple antigens, and improved vaccines are under development for cholera, influenza, and meningococcal disease. Major advances in molecular biology have enabled scientists to devise new approaches to the development of vaccines against diseases ranging from respiratory viral to enteric bacterial infections that continue to plague the world's population.
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PMID:Active immunization in the United States: developments over the past decade. 1158 89

In the last decade in Chile, there was a large reduction in the rate of communicable diseases, especially typhoid fever, and those preventable through the universal vaccination programs. Exceptions were hepatitis A and Pertussis. The reduction in tuberculosis, has lead the country to a threshold in which the elimination of tuberculosis as a public health problem is reachable. The HIV epidemic is still expanding, at higher rate among women and heterosexual men, keeping drug addiction as a low ranked risk factor. At the end of the century, universal or expanded access to HIV therapy was still not a reality. Cholera was a well controlled emerging infection, but Hantavirus infection has become a major threat in many regions. Syphilis and especially gonorrhea have decreased, but condyloma has increased dramatically. The nosocomial infection scenario has changed somehow, due to more severely ice and complex patients admitted to hospitals. Multiresistant nosocomial pathogens continue expanding (S aureus, fermentor and non fermentor gram negative rods, especially A baumannii). The country has been able to expand control programs to almost all hospitals. Antimicrobial resistance has continued growing. The massive and indiscriminate use of antibiotics, largely responsible for the resistance, grew worse until the sale of antimicrobials in pharmacies was restricted by law. This had a major impact, with important reduction in sales of most, but not all, antibiotics. The impact in resistance rate of this reduction, if any, has yet to be assessed.
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PMID:[Changes in the epidemiology of infectious diseases in Chile from 1990 to 2000]. 1209 99


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