UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following the introduction of whole-cell pertussis vaccines into the general population, the number of cases of Bordetella pertussis disease declined dramatically. As disease incidence declined, the public's concern for pertussis as a national health problem gradually waned. However, a shift in paradigm occurred, and various groups and the media began to voice their concerns regarding adverse events associated with whole-cell vaccines. These events provided an impetus for the expedited development of safer and as efficacious subunit acellular vaccines. Effective public health leadership, public advocacy, scientific ingenuity, and collaborative interactions between government, academia, and industry culminated in the licensure of acellular pertussis vaccines. In this article, emphasis is placed on conceptualizing how a national public health agenda was implemented that allowed better insight into various public health concerns related to the development and use of acellular pertussis vaccines, concerns that were eventually translated into concrete actions. Knowledge of the environment in which this occurred may play a major role in relating the pertussis experience to tuberculosis vaccine development.
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PMID:From pertussis to tuberculosis: what can be learned? 1087 5

The recent development of acellular pertussis vaccines has been a significant improvement in the conventional whole-cell diphtheria-pertussis-tetanus toxoid vaccines, but high production costs will limit its widespread use in developing countries. Since Mycobacterium bovis BCG vaccination against tuberculosis is used in most developing countries, a recombinant BCG-pertussis vaccine could be a more viable alternative. We have constructed recombinant BCG (rBCG) strains expressing the genetically detoxified S1 subunit of pertussis toxin 9K/129G (S1PT) in fusion with either the beta-lactamase signal sequence or the whole beta-lactamase protein, under control of the upregulated M. fortuitum beta-lactamase promoter, pBlaF*. Expression levels were higher in the fusion with the whole beta-lactamase protein, and both were localized to the mycobacterial cell wall. The expression vectors were relatively stable in vivo, since at two months 85% of the BCG recovered from the spleens of vaccinated mice maintained kanamycin resistance. Spleen cells from rBCG-S1PT-vaccinated mice showed elevated gamma interferon (IFN-gamma) and low interleukin-4 (IL-4) production, as well as increased proliferation, upon pertussis toxin (PT) stimulation, characterizing a strong antigen-specific Th1-dominant cellular response. The rBCG-S1PT strains induced a low humoral response against PT after 2 months. Mice immunized with rBCG-S1PT strains displayed high-level protection against an intracerebral challenge with live Bordetella pertussis, which correlated with the induction of a PT-specific cellular immune response, reinforcing the importance of cell-mediated immunity in the protection against B. pertussis infection. Our results suggest that rBCG-expressing pertussis antigens could constitute an effective, low-cost combined vaccine against tuberculosis and pertussis.
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PMID:Recombinant Mycobacterium bovis BCG expressing pertussis toxin subunit S1 induces protection against an intracerebral challenge with live Bordetella pertussis in mice. 1094

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

BCG, the attenuated strain of Mycobacterium bovis, has been widely used as a vaccine against tuberculosis and is thus an important candidate as a live carrier for multiple antigens. With the aim of developing a recombinant BCG (rBCG) vaccine against diphtheria, pertussis, and tetanus (DPT), we analyzed the potential of CRM(197), a mutated nontoxic derivative of diphtheria toxin, as the recombinant antigen for a BCG-based vaccine against diphtheria. Expression of CRM(197) in rBCG was achieved using Escherichia coli-mycobacterium shuttle vectors under the control of pBlaF*, an upregulated beta-lactamase promoter from Mycobacterium fortuitum. Immunization of mice with rBCG-CRM(197) elicited an anti-diphtheria toxoid antibody response, but the sera of immunized mice were not able to neutralize diphtheria toxin (DTx) activity. On the other hand, a subimmunizing dose of the conventional diphtheria-tetanus vaccine, administered in order to mimic an infection, showed that rBCG-CRM(197) was able to prime the induction of a humoral response within shorter periods. Interestingly, the antibodies produced showed neutralizing activity only when the vaccines had been given as a mixture in combination with rBCG expressing tetanus toxin fragment C (FC), suggesting an adjuvant effect of rBCG-FC on the immune response induced by rBCG-CRM(197). Isotype analysis of the anti-diphtheria toxoid antibodies induced by the combined vaccines, but not rBCG-CRM(197) alone, showed an immunoglobulin G1-dominant profile, as did the conventional vaccine. Our results show that rBCG expressing CRM(197) can elicit a neutralizing humoral response and encourage further studies on the development of a DPT vaccine with rBCG.
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PMID:Induction of neutralizing antibodies against diphtheria toxin by priming with recombinant Mycobacterium bovis BCG expressing CRM(197), a mutant diphtheria toxin. 1115 80

A cohort of 760 newborns was followed prospectively for 2 years to ascertain the time of administration of childhood vaccinations in rural Malawi and to study predictors of non-compliance with national vaccination recommendations. At 1 year of age, 99% of the infants were fully vaccinated against tuberculosis, 91% against polio, 90% against diphtheria, pertussis and tetanus and 64% against measles. At 2 years, the corresponding vaccination coverages were 99%, 93%, 93% and 84%. On average, all vaccinations were given 1-3 months later than recommended. Many of the delayed measles vaccinations were given during a separate vertical campaign, during which 25% of previously unvaccinated 21-23-month-old children were identified and immunized. Non-compliance with vaccination recommendations was associated with living in villages with no access to mobile vaccination teams, birth between April and June and birth at home. In this rural Malawian area, most vaccination services were functioning well. To increase measles vaccination coverage, regular outreach activities should be encouraged.
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PMID:Childhood immunization in rural Malawi: time of administration and predictors of non-compliance. 1121 69

In March 1999 armed conflict broke out in Kosova and about 900,000 ethnic Albanians were displaced. We reviewed the health care offered to the 945 Kosovan refugees who arrived in Ireland in 1999, which included screening for tuberculosis (TB) and hepatitis B. On arrival in Ireland 540 refugees had already received oral polio vaccine (57%), 512 diphtheria, tetanus, and acellular pertussis or diphtheria and tetanus vaccine (54%), 310 BCG (33%), 207 measles, mumps, and rubella vaccine (22%) and 60 Haemophilus influenzae type b (6%). Twelve refugees were diagnosed with TB. Twenty-six refugees were HBsAg positive (3%) and 168 were anti-HBcAg positive (18%). Organised screening of Kosovan refugees on a voluntary basis (uptake > 95%) revealed low percentages who had been immunised and relatively high rates of TB and hepatitis B. The provision of optimum immunisation, screening, and treatment services to address these issues requires substantial staffing and financial resources.
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PMID:Outcome of medical screening of Kosovan refugees in Ireland: 1999. 1128 Feb 62

The current EPI (Expanded Programme on Immunization) vaccines do not specifically target the organisms that lead to the two main causes of death in children - pneumonia and diarrhoea. This implies that the EPI vaccines will have only a modest effect on total child mortality. However, recent evidence suggests that measles and BCG vaccines dramatically reduce child mortality through nonspecific effects - that is, they reduce mortality from many causes, not just measles and tuberculosis. The combination of BCG at birth and measles vaccine at 6 months probably reduces total mortality to about one-third of its previous level. This means that immunization must now have the very highest priority. If we could improve immunization in Papua New Guinea so that all children received BCG, measles, diphtheria-pertussis-tetanus and polio vaccines, we would reduce child mortality from 120 to approximately 52 per 1000 livebirths - a truly spectacular reduction. The old polysaccharide pneumococcal vaccine is safe and effective and bulk purchases are likely to cost US$1 a dose or less. Further studies are needed of the effects of pneumococcal vaccine. Immunization of mothers and babies might reduce child mortality by 20%, at a cost of only US$83 per life saved. The available evidence suggests that one dose of pneumococcal vaccine given to every Papua New Guinean over 5 years of age every 5 years would save approximately 6600 lives a year and the vaccine would cost only US$121 per life saved. It will not be easy to achieve high immunization rates throughout Papua New Guinea. Vaccines will have to be given the highest possible priority, with curative medical services secondary to immunization. Health workers, government, the general population and overseas donors will have to be convinced of the very great benefits that will come from effective immunization. A sustained education campaign will be needed in addition to the establishment of an effective delivery system. The time has come for a radical shift in emphasis in Papua New Guinea: from hospitalization to immunization.
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PMID:Immunization--dramatic new evidence. 1296 96

Proteins of the Smr family are the smallest multidrug transporters, about 110 amino acids long, that extrude various drugs in exchange with protons, thereby rendering bacteria resistant to these compounds. One of these proteins, EmrE, is an Escherichia coli protein, which has been cloned based on its ability to confer resistance to ethidium and methyl viologen and which has been extensively characterized. More than 60 genes coding for Smr proteins have been identified in several bacteria based on amino acid sequence similarity to the emrE gene. In this work we have analyzed the sequence similarity among these homologues and identified some distinct signature sequence elements and several fully conserved residues. Five of these homologues, from human pathogens Mycobacterium tuberculosis, Bordetella pertussis, and Pseudomonas aeruginosa and from Escherichia coli, were cloned into an E. coli expression system. The proteins were further characterized and show varying degrees of methyl viologen uptake into proteoliposomes and [(3)H]TPP binding in solubilized membranes. The homologues can also form mixed oligomers with EmrE that exhibit intermediate binding characteristics. A comparative study of various homologous proteins provides a tool for deciphering structure-function relationship and monomer-monomer interaction in multidrug transporters and in membrane proteins in general.
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PMID:Functional analysis of novel multidrug transporters from human pathogens. 1157 48

The expanded program on immunization will soon celebrate its 25th anniversary. The original program included vaccination against diphtheria, tetanus, pertussis, poliomyelitis, measles, and tuberculoses. It was expanded to include first yellow fever and hepatitis B and later haemophilus. Results are mixed. Diphtheria was under control but has made a major comeback since vaccination was halted in eastern Europe. Tetanus in newborns should no longer be a public health problem by 2005. Control of pertussis has not been achieved because the vaccine has been unsuccessful in interrupting transmission. Poliomyelitis is no longer reported in the Americas. Hopefully transmission of the wild virus will be stopped by 2003 and total eradication of poliomyelitis will be achieved by 2005. For several reasons, there has been an alarming increase in tuberculosis with an estimated annual incidence of 5 million cases worldwide. Eradication of measles was achieved in the Americas in 2000 and is expected in the European region by 2007 and in the east Mediterranean area by 2010. Current data on yellow fever and hepatitis B is inadequate, these vaccination being still poorly implemented in endemic areas. A more widespread use of the vaccine will be needed. However spending cutbacks and changing priorities in the Health Ministries will require a renewal of commitment to this immunization policy.
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PMID:[The expanded program of vaccination: 25 years tomorrow]. 1158 77

The principal sulfatide of virulent Mycobacterium tuberculosis, sulfolipid-I (SL-I), both directly stimulates neutrophil superoxide (O(-)(2)) release and, at substimulatory concentrations, primes these cells for markedly enhanced oxidative responsiveness to other stimuli. The present study was undertaken to clarify the priming mechanisms by comparing cellular events following priming doses of SL-I with those following priming with N-formyl-methionyl-leucylphenylalanine (FMLP). We compared the involvement of the calcium cation (Ca(2+)), as well as membrane protein kinase C (PKC) activity and the translocation of NADPH oxidase-cytosolic cofactor effected by priming levels of the two agonists. The investigation led to two important conclusions. First, we clearly demonstrate that priming by both SL-I and FMLP results from activation of cellular processes that are not involved in direct oxidative activation. For example, whereas direct induction of O(-)(2) generation by FMLP and SL-I required increases in intracellular Ca(2+), an increase in intracellular calcium concentration ([Ca(2+)](i)) above basal levels was not required for priming. Second, we identified key differences in the cellular responses to priming doses of SL-I and FMLP. Whereas increased membrane PKC activity caused by priming doses of FMLP was only partially blocked by chelation of intracellular Ca(2+), Ca(2+) chelation completely inhibited the increase in membrane PKC activity caused by SL-I. NADPH oxidase-cytosolic factor translocation to plasma membranes was completely blocked by pertussis toxin when priming doses of SL-I were used. This guanine-nucleotide-binding protein inhibitor had no effect on FMLP-dependent translocation of the oxidase cofactors. The comparative approach introduced in this report provides a valuable and novel method to discern the complex interactions of various cellular processes that regulate the state of activation of stimulated cells. Copyright 1994 S. Karger AG, Basel
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PMID:Neutrophil Priming Mechanisms of Sulfolipid-I and N-Formyl-Methionyl-Leucyl-Phenylalanine. 1172 34

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