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Sample records for bcg immunisation delays

  1. Pattern and determinants of BCG immunisation delays in a sub-Saharan African community

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    Olusanya Bolajoko O

    2010-01-01

    Full Text Available Abstract Background Childhood immunisation is recognised worldwide as an essential component of health systems and an indispensable indicator of quality of care for vaccine-preventable diseases. While performance of immunisation programmes is more commonly measured by coverage, ensuring that every child is immunised at the earliest/appropriate age is an important public health goal. This study therefore set out to determine the pattern and predictors of Bacille de Calmette-Guérin (BCG immunisation delays in the first three months of life in a Sub-Saharan African community where BCG is scheduled at birth in order to facilitate necessary changes in current policy and practices for improved services. Methods A cross-sectional study in which immunisation delays among infants aged 0-3 months attending community-based BCG clinics in Lagos, Nigeria over a 2-year period from July 2005 to June 2007 were assessed by survival analysis and associated factors determined by multivariable logistic regression. Population attributable risk (PAR was computed for the predictors of delays. Results BCG was delayed beyond three months in 31.6% of all eligible infants. Of 5171 infants enrolled, 3380 (65.4% were immunised within two weeks and a further 1265 (24.5% by six weeks. A significantly higher proportion of infants born in hospitals were vaccinated in the first six weeks compared to those born outside hospitals. Undernourishment was predictive of delays beyond 2 and 6 weeks while treated hyperbilirubinaemia was associated with decreased odds for any delays. Lack of antenatal care and multiple gestations were also predictive of delays beyond 6 weeks. Undernourishment was associated with the highest PAR for delays beyond 2 weeks (18.7% and 6 weeks (20.8%. Conclusions BCG immunisation is associated with significant delays in this setting and infants at increased risk of delays can be identified and supported early possibly through improved maternal uptake of

  2. Rabbits immunised with recombinant BCG expressing the cottontail rabbit papillomavirus (CRPV) L2E7E2 genes induces regression of established papillomas.

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    Govan, V A; Williamson, A-L

    2007-07-01

    We previously demonstrated in a cottontail rabbit papillomavirus (CRPV) challenge model that recombinant Bacille Calmette-Guerin (rBCG) could potentially be used as a prophylactic vaccine vehicle to deliver papillomavirus proteins. In this study we investigated whether regression of CRPV-induced papillomas could be achieved following immunisation of out-bred New Zealand White rabbits with rBCG expressing CRPVL2, CRPVE2, CRPVE7 or CRPVL2E7E2 proteins. Rabbits immunised with rBCG/CRPVL2E7E2 had papillomas that were largely suppressed and were significantly smaller compared to the rBCG negative control group (Prabbits immunised with rBCG/CRPVL2E7E2 had papillomas that completely regressed 1.5 weeks post third immunisation. Rabbits immunised with rBCG/CRPVL2, rBCG/CRPVE7, or rBCG/CRPVE2 had papillomas that were significantly smaller than the negative control rabbits (PBCG could probably be used as a vaccine delivery vehicle for human papillomavirus proteins as a possible therapeutic vaccine.

  3. Adverse events following immunisation with bacille Calmette-Guérin vaccination: baseline data to inform monitoring in Australia following introduction of new unregistered BCG vaccine.

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    Hendry, Alexandra J; Dey, Aditi; Beard, Frank H; Khandaker, Gulam; Hill, Richard; Macartney, Kristine K

    2016-12-24

    In recent years there has been a global shortage of bacille Calmette-Guérin (BCG) vaccine and, from September 2012, unregistered vaccines have needed to be used in Australia (a Danish product initially until the end of 2015, and a Polish product used in some jurisdictions from early 2016). We examined rates and types of adverse events following immunisation (AEFI) with BCG vaccine reported to the Therapeutic Goods Administration between 2009 and 2014 in children aged less than 7 years. Reporting rates of AEFI with BCG vaccine increased from 87 per 100,000 doses (registered Sanofi Pasteur product) in 2009 to 201 per 100,000 doses (unregistered Danish Statens Serum Institute product) in 2014, with Victoria having the highest rate each year. Substantial variation between jurisdictions exists, suggesting differential reporting of BCG vaccine doses administered and/or BCG vaccine-related AEFI. The most commonly reported reactions were abscess (31%), injection site reaction (27%) and lymphadenopathy/lymphadenitis (17%). This study provides baseline data on BCG vaccine safety to inform surveillance. Given the current use of unregistered vaccines in the context of vaccine supply issues, improved recording of both administered BCG vaccine doses and the reporting of BCG vaccine-related AEFI are required to facilitate close monitoring of vaccine safety.

  4. A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guérin (BCG immunisation [ISRCTN32849447

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    Nampijja Margaret

    2005-12-01

    Full Text Available Abstract Background Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown. Methods In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ and interleukin (IL-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP of Mycobacterium tuberculosis were measured in a whole blood assay. We analysed results for binary variables using χ2 tests and logistic regression. We analysed continuous variables using Wilcoxon's tests. Results Maternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021. Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013. Maternal albendazole tended to reduce these effects. Conclusion Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.

  5. Bacillus Calmette-Guérin immunisation at birth and morbidity among Danish children

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    Thøstesen, Lisbeth Marianne; Nissen, Thomas Nørrelykke; Kjærgaard, Jesper

    2015-01-01

    BACKGROUND: Studies from low-income countries report positive non-specific effects of early Bacillus Calmette-Guérin (BCG) immunisation on childhood health and survival. Neonatal immunisation with BCG may prime the immune system and offer partial protection against other infectious and possibly...

  6. Maternal immunisation

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    Verweij, Marcel; Lambach, Philipp; Ortiz, Justin R.; Reis, Andreas

    2016-01-01

    There has been increased interest in the potential of maternal immunisation to protect maternal, fetal, and infant health. Maternal tetanus vaccination is part of routine antenatal care and immunisation campaigns in many countries, and it has played an important part in the reduction of maternal and

  7. Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.

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    Gillian S Dean

    Full Text Available The incidence of bovine tuberculosis (bTB in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission.

  8. Annual immunisation coverage report, 2010.

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    Hull, Brynley; Dey, Aditi; Menzies, Rob; McIntyre, Peter

    2013-03-31

    This, the fourth annual immunisation coverage report, documents trends during 2010 for a range of standard measures derived from Australian Childhood Immunisation Register (ACIR) data. These include coverage at standard age milestones and for individual vaccines included on the National Immunisation Program (NIP). For the first time, coverage from other sources for adolescents and the elderly are included. The proportion of children 'fully vaccinated' at 12, 24 and 60 months of age was 91.6%, 92.1% and 89.1% respectively. For vaccines available on the NIP but not currently assessed for 'fully immunised' status or for eligibility for incentive payments (rotavirus and pneumococcal at 12 months and meningococcal C and varicella at 24 months) coverage varied. Although pneumococcal vaccine had similar coverage at 12 months to other vaccines, coverage was lower for rotavirus at 12 months (84.7%) and varicella at 24 months (83.0%). Overall coverage at 24 months of age exceeded that at 12 months of age nationally and for most jurisdictions, but as receipt of varicella vaccine at 18 months is excluded from calculations, this represents delayed immunisation, with some contribution from immunisation incentives. The 'fully immunised' coverage estimates for immunisations due by 60 months increased substantially in 2009, reaching almost 90% in 2010, probably related to completed immunisation by 60 months of age being introduced in 2009 as a requirement for GP incentive payments. As previously documented, vaccines recommended for Indigenous children only (hepatitis A and pneumococcal polysaccharide vaccine) had suboptimal coverage at around 57%. Delayed receipt of vaccines by Indigenous children at the 60-month milestone age improved from 56% to 62% but the disparity in on-time vaccination between Indigenous and non-Indigenous children at earlier age milestones did not improve. Coverage data for human papillomavirus (HPV)from the national HPV register are consistent with high

  9. Randomized trial of BCG vaccination at birth to low-birth-weight children

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    Aaby, Peter; Roth, Adam Anders Edvin; Ravn, Henrik

    2011-01-01

    Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG.......Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG....

  10. Optimization of cell-wall skeleton derived from Mycobacterium bovis BCG Tokyo 172 (SMP-105) emulsion in delayed-type hypersensitivity and antitumor models.

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    Miyauchi, M; Murata, M; Fukushima, A; Sato, T; Nakagawa, M; Fujii, T; Koseki, N; Chiba, N; Kashiwazaki, Y

    2012-08-01

    Cell-wall skeleton prepared from Mycobacterium bovis BCG (BCG-CWS) is known as a potent adjuvant and has been shown to possess antitumor activity in many non-clinical and clinical studies. As there are no approved BCG-CWS formulations for cancer therapy, we investigated the potential for cancer immunotherapy of SMP-105, our originally produced BCG-CWS. For optimizing SMP-105 emulsion, we compared the effects of drakeoland squalane-based SMP-105 emulsions on IFN-γ production in rats and evaluated their ability to induce skin reaction in guinea pigs. Both emulsions had the same activity in both experiments. We selected squalane as base material and produced two types of squalane-based formulations (vialed emulsion and pumped emulsion) that can easily be prepared as oil-in-water emulsions. Although the vialed emulsion showed the same pattern of distribution as a usual homogenized emulsion, the pumped emulsion showed more uniform distribution than the other two emulsions. Whereas both emulsions enhanced strong delayed type hypersensitivity (DTH) reaction in a mouse model, the pumped emulsion induced slightly smaller edema. Data on oil droplet size distribution suggest that few micrometer oil droplet size might be appropriate for oil-in-water microemulsion of SMP-105. The antitumor potency of SMP-105 emulsion was stronger than that of some of the launched toll-like receptor (TLR) agonists (Aldara cream, Picibanil, and Immunobladder). Aldara and Picibanil showed limited antitumor effectiveness, while Immunobladder had almost the same effect as SMP-105 at the highest dose, but needed about 10 times the amount of SMP-105. These findings first indicate that SMP-105 has great potential in cancer immunotherapy.

  11. Immunisation of colorectal cancer patients with autologous tumour cells

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    Diederichsen, Axel Cosmus Pyndt; Stenholm, A C; Kronborg, O

    1998-01-01

    Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression...

  12. BCG LYMPHADENITIS

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    Vijayakumar

    2014-08-01

    Full Text Available Background: The World Health Organization (WHO has recommended Bacillus Calmette-Guerin (BCG vaccination as a part of the global expanded program for immunization. Although the BCG vaccine is usually a safe vaccine, a number of complications with lymphadenitis being the most common complication, can occur. AIM: The aim of the present study was to evaluate the clinical presentation and the histomorphological features of BCG adenitis in children. RESULTS: A total of 60 patients with BCG lymphadenitis presented between June 2010 and December 2013. The most common age of presentation was 3 months. In the majority (50 of the cases, the lymphadenitis involved ipsilateral left axillary nodes. Other sites of involvement included the left supraclavicular lymph nodes in 5 (8.3% patients, and both the left axillary and supraclavicular lymph nodes were involved in 5 cases (8.3%. All the patients had history of BCG vaccination prior to the onset of lymphadenitis. CONCLUSION: Diagnosis of BCG lymphadenitis is clinical. Parental education and awareness among paramedical personnel, including general practitioners, is essential so that prompt recognition and management of BCG adenitis can be ensured.

  13. Immunisation coverage, 2012.

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    Hull, Brynley P; Dey, Aditi; Menzies, Rob I; Brotherton, Julia M; McIntyre, Peter B

    2014-09-30

    This, the 6th annual immunisation coverage report, documents trends during 2012 for a range of standard measures derived from Australian Childhood Immunisation Register (ACIR) data, and National Human Papillomavirus (HPV) Vaccination Program Register data. These include coverage at standard age milestones and for individual vaccines included on the National Immunisation Program (NIP) and coverage in adolescents and adults. The proportion of Australian children 'fully vaccinated' at 12, 24 and 60 months of age was 91.7%, 92.5% and 91.2%, respectively. For vaccines available on the NIP but not assessed during 2012 for 'fully vaccinated' status or for eligibility for incentive payments (rotavirus and pneumococcal at 12 months and meningococcal C and varicella at 24 months) coverage varied. Although pneumococcal vaccine had similar coverage at 12 months to other vaccines, coverage was lower for rotavirus at 12 months (83.6%) and varicella at 24 months (84.4%). Although 'fully vaccinated' coverage at 12 months of age was lower among Indigenous children than non-Indigenous children in all jurisdictions, the extent of the difference varied, reaching a 15 percentage point differential in South Australia but only a 0.4 percentage point differential in the Northern Territory. Overall, Indigenous coverage at 24 months of age exceeded that at 12 months of age nationally and for all jurisdictions, but as receipt of varicella vaccine at 18 months is excluded from calculations, this represents delayed immunisation, with some contribution from immunisation incentives. The 'fully vaccinated' coverage estimates for vaccinations due by 60 months of age for Indigenous children exceeded 90% at 91% in 2012. Unlike in 2011, at 60 months of age, there was no dramatic variation in coverage between Indigenous and non-Indigenous children for individual jurisdictions. As previously documented, vaccines recommended for Indigenous children only, hepatitis A and pneumococcal vaccine, had

  14. Impact of conflict on infant immunisation coverage in Afghanistan: a countrywide study 2000–2003

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    Seino Kaoruko

    2007-06-01

    Full Text Available Abstract Background Infant immunisation is an effective public health intervention to reduce the morbidity and mortality of vaccine preventable diseases. However, some developing countries fail to achieve desirable vaccination coverage; Afghanistan is one such country. The present study was performed to evaluate the progress and variation in infant immunisation coverage by district and region in Afghanistan and to assess the impact of conflict and resource availability on immunisation coverage. Results This study analysed reports of infant immunisation from 331 districts across 7 regions of Afghanistan between 2000 and 2003. Geographic information system (GIS analysis was used to visualise the distribution of immunisation coverage in districts and to identify geographic inequalities in the process of improvement of infant immunisation coverage. The number of districts reporting immunisation coverage increased substantially during the four years of the study. Progress in Bacillus Calmette-Guerin (BCG immunisation coverage was observed in all 7 regions, although satisfactory coverage of 80% remained unequally distributed. Progress in the third dose of Diphtheria-Pertussis-Tetanus (DPT3 immunisation differed among regions, in addition to the unequal distribution of immunisation coverage in 2000. The results of multivariate logistic regression analysis indicated a significant negative association between lack of security in the region and achievement of 80% coverage of immunisation regardless of available resources for immunisation, while resource availability showed no relation to immunisation coverage. Conclusion Although progress was observed in all 7 regions, geographic inequalities in these improvements remain a cause for concern. The results of the present study indicated that security within a country is an important factor for affecting the delivery of immunisation services.

  15. Ethical issues in immunisation.

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    Isaacs, David; Kilham, Henry; Leask, Julie; Tobin, Bernadette

    2009-01-29

    Discussions about current and future immunisation programmes raise novel questions about familiar ethical issues. Two sets of ethical issues dominate these discussions. The first is the issue of compulsory immunisation: what should be done about parents who fail to immunise their children? The second is: given competing demands on health care budgets, how should principles of justice in access and distribution inform vaccination programmes? This paper considers these two issues in the light of traditional ethical principles. With respect to the first, we argue that compulsion is justified only in cases in which we know with practical certainty that parental failure to immunise puts their own child or other children at high risk of severe illness. We also argue that the state should compensate those who suffer vaccine-related injury. With respect to the second, we claim that allocating resources according to health care need requires establishing priorities between public health programmes such as immunisation and other treatment programmes.

  16. Immunisation hotline calls as five-in-one vaccine introduced.

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    Fisher-Jeffes, Lisa; Finlay, Fiona

    2006-04-01

    Announcement of the introduction of the five-in-one vaccine (DTaP/IPV/Hib) into the primary immunisation schedule was made on 9 August 2004. In this study all calls to the immunisation hotline were recorded between 9 August 2004 and 19 November 2004, noting who called and the nature of their enquiry. A total of 208 calls were received during the study period, and of these 23 (11.1%) related to the new vaccine. Calls were from parents (10/23, 43%), health visitors (9/23, 39%) and practice nurses (3/23, 13%). A variety of themes were covered in calls including local availability of the five-in-one vaccine, vaccine safety, mercury content and efficacy. Calls not connected with the new vaccine concerned mostly adolescent MMR (17.3%) as there was a local mumps epidemic. Others related to clarification of a child's immunisation status (13.5%), primary MMR immunisation (13.5%), vaccination scheduling or administration difficulties (12%), other schedule (12.5%) and non-schedule vaccines (2.4%), vaccine reactions (2.4%), travel vaccines (6%), BCG (6%), and a few miscellaneous queries (3%). Overall questions about the new five-in-one vaccine accounted for an extra 23 calls to the immunisation hotline during the study period (11.1% of calls).

  17. Immunisation in the current management of cystic fibrosis patients

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    Malfroot, Anne; Adam, Georgios; Ciofu, Oana;

    2005-01-01

    for palivizumab in CF as an alternative but expensive prophylaxis. Anti-bacterial vaccinations protecting directly against Pseudomonas aeruginosa colonisation are promising for the future, potential candidates are currently being assessed in phase III clinical trials. More studies are needed to complete......Although no special recommendations exist, clearly patients with cystic fibrosis (CF) can benefit from immunisation. We reviewed the literature regarding vaccination in CF and other chronic diseases. CF subjects should follow national immunisation programmes without delay to obtain optimal...

  18. BCG coverage and barriers to BCG vaccination in Guinea-Bissau

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    Thysen, Sanne Marie; Byberg, Stine; Pedersen, Marie;

    2014-01-01

    in selected intervention regions. Factors associated with delayed BCG vaccination were evaluated using logistic regression models. Coverage between intervention and control regions were evaluated in log-binomial regression models providing prevalence ratios. RESULTS: Among 3951 children born in 2010...

  19. Should childhood immunisation be compulsory?

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    Bradley, P

    1999-08-01

    Immunisation is offered to all age groups in the UK, but is mainly given to infants and school-age children. Such immunisation is not compulsory, in contrast to other countries, such as the United States. Levels of immunisation are generally very high in the UK, but the rates of immunisation vary with the public perception of the risk of side effects. This article discusses whether compulsory vaccination is acceptable by considering individual cases where parents have failed to give consent or have explicitly refused consent for their children to be immunised. In particular, the rights of: a parent to rear his/her child according to his/her own standards; the child to receive health care, and the community to be protected from vaccine-preventable infectious disease are considered. The conclusion of the article is that compulsory vaccination cannot, with very few exceptions, be justified in the UK, in view of the high levels of population immunity which currently exist.

  20. Oral delivery of BCG Moreau Rio de Janeiro gives equivalent protection against tuberculosis but with reduced pathology compared to parenteral BCG Danish vaccination.

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    Clark, Simon O; Kelly, Dominic L F; Badell, Edgar; Castello-Branco, Luiz Roberto; Aldwell, Frank; Winter, Nathalie; Lewis, David J M; Marsh, Philip D

    2010-10-08

    There is a need for an improved vaccine to better control human tuberculosis (TB), as the only currently available TB vaccine, bacillus Calmette-Guerin (BCG) delivered parenterally, offers variable levels of efficacy. Therefore, recombinant strains expressing additional antigens are being developed alongside alternative routes to parenteral delivery. There is strong evidence that BCG Moreau (RdJ) is a safe and effective vaccine in humans when given by the oral route. This study compared the efficacy of a single oral dose of wild type BCG Moreau Rio de Janeiro (RdJ), or a recombinant RdJ strain expressing Ag85B-ESAT6 fusion protein, formulated with and without lipid to enhance oral delivery, with subcutaneous BCG Danish 1331 and saline control groups in a guinea pig aerosol infection model of pulmonary tuberculosis. Protection was measured as survival at 30 weeks post-challenge and reduced bacterial load and histopathology in lungs and spleen. Results showed that a single oral dose of BCG Moreau (RdJ) or recombinant BCG Moreau (RdJ)-Ag85B-ESAT6, formulated with or without lipid, gave protection equivalent to subcutaneously delivered BCG Danish in the 30 weeks post-challenge survival study. The orally delivered vaccines gave reduced pathology scores in the lungs (three of the four formulations) and spleens (all four formulations) compared to subcutaneously delivered BCG Danish. The oral wild type BCG Moreau (RdJ) in lipid and the unformulated oral wild type BCG Moreau (RdJ) vaccine also gave statistically lower bacterial loads in the lungs and spleens, respectively, compared to subcutaneously delivered BCG Danish. This study provides further evidence to show that lipid formulation does not impair vaccine efficacy and may enhance the delivery and stability of oral vaccines intended for use in countries with poor health infrastructure. Oral delivery also avoids needles (and associated cross-infection risks) and immunisation without the need for specially trained

  1. Immunisation Guidelines for Ireland (2008)

    OpenAIRE

    Department of Health

    2008-01-01

    Immunisation Guidelines for Ireland (2008) This revised report on immunisation guidelines for Ireland has been prepared with the assistance of an active Committee from associated disciplines in Paediatrics, Infectious Diseases, General Practice, Public Health, Microbiology, Occupational Health, Travel Medicine and the Irish Medicines Board. The report itself continues to be simple and concise in design and of course does not claim to contain all information on any pharmacological material....

  2. Aerosol immunisation for TB: matching route of vaccination to route of infection.

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    Manjaly Thomas, Zita-Rose; McShane, Helen

    2015-03-01

    TB remains a very significant global health burden. There is an urgent need for better tools for TB control, which include an effective vaccine. Bacillus Calmette-Guérin (BCG), the currently licensed vaccine, confers highly variable protection against pulmonary TB, the main source of TB transmission. Replacing BCG completely or boosting BCG with another vaccine are the two current strategies for TB vaccine development. Delivering a vaccine by aerosol represents a way to match the route of vaccination to the route of infection. This route of immunisation offers not only the scientific advantage of delivering the vaccine directly to the respiratory mucosa, but also practical and logistical advantages. This review summarises the state of current TB vaccine candidates in the pipeline, reviews current progress in aerosol administration of vaccines in general and evaluates the potential for TB vaccine candidates to be administered by the aerosol route.

  3. Maternal BCG scar is associated with increased infant proinflammatory immune responses

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    Mawa, Patrice Akusa; Webb, Emily L.; Filali-Mouhim, Abdelali; Nkurunungi, Gyaviira; Sekaly, Rafick-Pierre; Lule, Swaib Abubaker; Prentice, Sarah; Nash, Stephen; Dockrell, Hazel M.; Elliott, Alison M.; Cose, Stephen

    2017-01-01

    Introduction Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-induced responses in Ugandan infants. Material and methods Maternal and cord blood samples from 29 mother-infant pairs were stimulated with innate stimuli for 24 h and cytokines and chemokines in supernatants were measured using the Luminex® assay. The associations between maternal latent Mycobacterium tuberculosis infection (LTBI), maternal BCG scar (adjusted for each other’s effect) and infant responses were examined using linear regression. Principal Component Analysis (PCA) was used to assess patterns of cytokine and chemokine responses. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n = 42) and six (n = 51) weeks after BCG immunisation using microarray. Results Maternal LTBI was positively associated with infant IP-10 responses with an adjusted geometric mean ratio (aGMR) [95% confidence interval (CI)] of 5.10 [1.21, 21.48]. Maternal BCG scar showed strong and consistent associations with IFN-γ (aGMR 2.69 [1.15, 6.17]), IL-12p70 (1.95 [1.10, 3.55]), IL-10 (1.82 [1.07, 3.09]), VEGF (3.55 [1.07, 11.48]) and IP-10 (6.76 [1.17, 38.02]). Further assessment of the associations using PCA showed no differences for maternal LTBI, but maternal BCG scar was associated with higher scores for principal component (PC) 1 (median level of scores: 1.44 in scar-positive versus −0.94 in scar-negative, p = 0.020) in the infants. PC1 represented a controlled proinflammatory response. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation. Conclusions

  4. Coverage and timing of children's vaccination: an evaluation of the expanded programme on immunisation in The Gambia.

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    Susana Scott

    Full Text Available OBJECTIVE: To evaluate the coverage and timeliness of the Expanded Programme on Immunisation (EPI in The Gambia. METHODS: Vaccination data were obtained between January 2005 and December 2012 from the Farafenni Health and Demographic Surveillance System (FHDSS, the Basse Health and Demographic Surveillance System (BHDSS, the Kiang West Demographic surveillance system (KWDSS, a cluster survey in the more urban Western Health Region (WR and a cross sectional study in four clinics in the semi-urban Greater Banjul area of WR. Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and to assess timeliness to vaccination. FINDINGS: BCG vaccine uptake was over 95% in all regions. Coverage of DPT1 ranged from 93.2% in BHDSS to 99.8% in the WR. Coverage decreased with increasing number of DPT doses; DPT3 coverage ranged from 81.7% in BHDSS to 99.0% in WR. Measles vaccination coverage ranged from 83.3% in BHDSS to 97.0% in WR. DPT4 booster coverage was low and ranged from 43.9% in the WR to 82.8% in KWDSS. Across all regions, delaying on previous vaccinations increased the likelihood of being delayed for the subsequent vaccination. CONCLUSIONS: The Gambia health system achieves high vaccine coverage in the first year of life. However, there continues to be a delay to vaccination which may impact on the introduction of new vaccines. Examples of effectively functioning EPI programmes such as The Gambia one may well be important models for other low income countries struggling to achieve high routine vaccination coverage.

  5. Immunisation status in inner London primary schools.

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    Bedford, H E; Masters, J I; Kurtz, Z

    1992-01-01

    In one inner London district health authority, the immunisation status of children attending their routine school entry health interview was reviewed over four terms. During the course of these interviews, school nurses completed a questionnaire with parents that asked for their child's immunisation history and details of family and social background. Parental reporting of immunisation history was compared with district health authority records. Only 56% of children reviewed were found to be ...

  6. Immunisation in a curative setting

    DEFF Research Database (Denmark)

    Kofoed, Poul-Erik; Nielsen, B; Rahman, A K

    1990-01-01

    OBJECTIVE: To study the uptake of vaccination offered to women and children attending a curative health facility. DESIGN: Prospective survey over eight months of the uptake of vaccination offered to unimmunised women and children attending a diarrhoeal treatment centre as patients or attendants...... of women and children who were unimmunised or incompletely immunised was calculated and the percentage of this target population accepting vaccination was recorded. RESULTS: 7530 (84.2%) Of 8944 eligible children and 7730 (40.4%) of 19,138 eligible women were vaccinated. Of the children, 63.8% were boys...

  7. Immunisation issues for Indigenous Australian children.

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    Menzies, Robert; Andrews, Ross

    2014-10-01

    Vaccination has provided major benefits to the health of indigenous children in the face of continuing poorer socioeconomic conditions but several issues have been identified for improvement. While indigenous children are vaccinated at high rates for the standard schedule vaccines, vaccination is more commonly delayed. Coverage for 'targeted' vaccines is substantially lower, and data on coverage for indigenous adolescents is non-existent. Improved identification of indigenous clients by immunisation providers and the expansion of the childhood register are required. The progressive removal of early-acting Haemophilus influenzae type b vaccines from schedules for indigenous children because of an international shortage raises the risk of disease re-emergence and highlights the need for vigilant surveillance including carriage. The expanded use of existing vaccines (influenza) and early adoption of new vaccines (higher valency pneumococcal conjugates) are needed to maximise benefits, in particular the potential to impact on non-invasive disease such as otitis media and non-bacteraemic pneumonia that are so prevalent in indigenous children.

  8. Influencing factors in MMR immunisation decision making.

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    Hill, Marie C; Cox, Carol L

    Immunisation decision making is not a straightforward process for parents. Many factors influence parental decision making on whether they immunise their child with the measles, mumps and rubella (MMR) vaccine. The feasibility study described in this article provides insight into influencing factors associated with decisions regarding the immunisation of children by parents. The study findings suggest that the practice nurse is a credible source of information for parents seeking informed decision making. At a time when the incidence of measles and mumps is rising in the UK, the provision of appropriate information by the practice nurse has the potential to increase uptake of the MMR vaccine.

  9. Feeling bad about immunising our children.

    Science.gov (United States)

    Wroe, Abigail L; Bhan, Angela; Salkovskis, Paul; Bedford, Helen

    2005-02-10

    Uptake of MMR vaccinations is as low as 60% in some parts of the UK. This poses a serious public health issue. This longitudinal study investigates parental decisions about MMR and single vaccinations. Parents (n=114) rated their perceptions of the benefits and risks of immunisation, and emotion-related variables; and were followed up to ask their final immunisation decision. Analyses demonstrated that parental decisions were explained by emotion-related variables, specifically anticipated responsibility and regret. It was concluded that parents' decisions about MMR are strongly influenced by the idea than harm that occurs as a result of deciding to immunise (commission) is less acceptable than harm that occurs as a result of deciding not to immunise (omission) (known as 'omission bias').

  10. Tuberculin reaction and BCG scar

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Biering-Sørensen, Sofie; Aaby, Peter;

    2015-01-01

    Abstract Objective To test the hypothesis that having a scar and a positive tuberculin skin test (TST) response after vaccination with Bacille Calmette–Guérin (BCG) is associated with reduced infant mortality. Methods We studied cohorts of 2709 normal-birthweight (NBW) and 1102 low-birthweight (LBW......) infants in Guinea-Bissau. Children were enrolled in randomised trials between year 2002 and 2008 and received BCG vaccination at birth. BCG scars and TST responses were assessed at 2 and 6 months of age. The infants were followed for mortality to 12 months of age, and survival was analysed using Cox...... regression. Results At age 2 months, 88% of NBW children and 91% of LBW children had a BCG scar, and 36% and 17% had a TST response, respectively. The LBW infants had nearly twofold higher mortality (4.5%) than the NBW infants (2.8%) between 2 and 12 months of age. In the LBW cohort, the adjusted mortality...

  11. Ultrasonographic features of BCG lymphadenitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Do Youn; Lee, Sun Wha; Hwang, Ji Young [College of Medicine, Ewha Womans University, Seoul (Korea, Republic of)

    2005-07-15

    To evaluate the ultrasonographic findings of BCG lymphadenitis complicated by BCG vaccination in children. Ultrasonography was performed for 22 cases of BCG lymphadenitis in 21 patients who were diagnosed by clinical (n=10) or pathological (n=11) examinations. Their age ranged from 4 months to 3 years (mean age; 14 months). We retrospectively analyzed the ultrasonographic findings for location, multiplicity, size, shape, margin, echogenecity, posterior enhancement, calcifications, inner anechoic portion and Doppler pattern of the BCG lymphadenitis. The BCG lymphadenitis was found at the axillary area in 15 cases (68%) and at the supraclavicular area in 7 cases (32%). There were ten cases (45%) of solitary lesion and 12 cases (55%) of multiple conglomerated lesions. The maximum diameter ranged from about 0.9 cm to 3.2 cm. The BCG lymphadenitis showed as round (82%), well defined (86%), or heterogeneous hypoechoic (68%) lesions with posterior enhancement (78%). Calcifications were found in 6 cases (27%) and 5 cases (83%) had been vaccinated more than 5 months ago. There were eccentric inner anechoic portions in 16 cases (73%), which were pathologically confirmed as having caseating necrosis. There were increased Doppler flow patterns in 15 cases (68%); 4 cases (18%) were of the central type, 6 cases (27%) were of the peripheral type and 5 cases (23%) were of mixed type. BCG lymphadenitis is frequently located at the axillary area adjacent to a vaccination site. The ultrasonographic findings of BCG lymphadenitis are well-defined, round, heterogeneously hypoechoic lesions with posterior enhancement, calcifications and inner eccentric anechoic portion.

  12. Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

    Directory of Open Access Journals (Sweden)

    Mogens Helweg Claesson

    2011-01-01

    Full Text Available A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell Bordetella pertussis (DTwP. In contrast, similar studies suggest that many African females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence both the deleterious and beneficial nonspecific effects of immunisation.

  13. Immunising Children in Primary Care in the UK--What Are the Concerns of Principal Immunisers?

    Science.gov (United States)

    Maconachie, Moira; Lewendon, Gill

    2004-01-01

    Objective: To determine the levels of concern about risks associated with childhood immunisations among principal immunisers in general practice. Design: Self-administered postal questionnaire survey. Setting: South & West Devon Health Authority. Participants: Eighty-eight/102 general practices: 78 practice nurses, 7 general practitioners, 3…

  14. Uptake of newly introduced universal BCG vaccination in newborns.

    LENUS (Irish Health Repository)

    Braima, O

    2010-06-01

    Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

  15. Uptake of newly introduced universal BCG vaccination in newborns.

    LENUS (Irish Health Repository)

    Braima, O

    2012-01-31

    Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

  16. Immunisation coverage annual report, 2011.

    Science.gov (United States)

    Hull, Brynley P; Dey, Aditi; Menzies, Rob I; Brotherton, Julia M; McIntyre, Peter B

    2013-12-31

    This, the 5th annual immunisation coverage report, documents trends during 2011 for a range of standard measures derived from Australian Childhood Immunisation Register data, and National Human Papillomavirus (HPV) Vaccination Program Register data. The proportion of children 'fully vaccinated' at 12, 24 and 60 months of age was 91.4%, 92.2% and 89.5% respectively. Although pneumococcal vaccine had similar coverage at 12 months to other vaccines, coverage was lower for rotavirus at 12 months (83.8%) and varicella at 24 months (83.9%). By late 2011, the percentage of children who received the 1st dose of DTPa vaccine dose at less than 8 weeks of age was greater than 50% in 3 jurisdictions, the Australian Capital Territory, Victoria, and Queensland and at 70% for New South Wales and Tasmania. Although coverage at 12 months of age was lower among Indigenous children than non-Indigenous children in all jurisdictions, the extent of the difference varied. Overall, coverage at 24 months of age exceeded that at 12 months of age nationally. At 60 months of age, there was dramatic variation between individual jurisdictions, ranging from coverage 8% lower in Indigenous children in South Australia to 6% higher in the Northern Territory. As previously documented, vaccines recommended for Indigenous children only (hepatitis A and pneumococcal polysaccharide vaccine) had suboptimal coverage at 60% and 68%, respectively. On-time receipt (before 49 months of age) of vaccines by Indigenous children at the 60-month milestone age improved between 2010 (18%) and 2011 (19%) but the disparity in on-time vaccination between Indigenous and non-Indigenous children increased at all 3 age milestones. The percentage of vaccine objectors in 2011 (1.7%) has increased from 2007 when it was 1.1%. Coverage data for the 3rd dose of HPV from the national HPV register in the school catch up program was 71% but was substantially lower for the catch-up program for women outside school (39

  17. Determinants of childhood immunisation coverage in urban poor settlements of Delhi, India: a cross-sectional study

    Science.gov (United States)

    Devasenapathy, Niveditha; Ghosh Jerath, Suparna; Sharma, Saket; Allen, Elizabeth; Shankar, Anuraj H; Zodpey, Sanjay

    2016-01-01

    Objectives Aggregate data on childhood immunisation from urban settings may not reflect the coverage among the urban poor. This study provides information on complete childhood immunisation coverage among the urban poor, and explores its household and neighbourhood-level determinants. Setting Urban poor community in the Southeast district of Delhi, India. Participants We randomly sampled 1849 children aged 1–3.5 years from 13 451 households in 39 clusters (cluster defined as area covered by a community health worker) in 2 large urban poor settlements. Of these, 1343 completed the survey. We collected information regarding childhood immunisation (BCG, oral polio vaccine, diphtheria–pertussis–tetanus vaccine, hepatitis B and measles) from vaccination cards or mothers’ recall. We used random intercept logistic regression to explore the sociodemographic determinants of complete immunisation. Results Complete immunisation coverage was 46.7% and 7.5% were not immunised. The odds of complete vaccination (OR, 95% CI) were lower in female children (0.70 (0.55 to 0.89)) and Muslim households (0.65 (0.45 to 0.94)). The odds of complete vaccination were higher if the mother was literate (1.6 (1.15 to 2.16)), if the child was born within the city (2.7 (1.97 to 3.65)), in a health facility ( 1.5 (1.19 to 2.02)), belonged to the highest wealth quintile (compared with the poorest; 2.46 (1.5 to 4.02)) or possessed a birth certificate (1.40 (1.03 to 1.91)). Cluster effect due to unmeasured neighbourhood factors expressed as median OR was 1.32. Conclusions Immunisation coverage in this urban poor area was much lower than that of regional surveys reporting overall urban data. Socioeconomic status of the household, female illiteracy, health awareness and gender inequality were important determinants of coverage in this population. Hence, in addition to enhancing the infrastructure for providing mother and child services, efforts are also needed to address these issues in

  18. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, A R;

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...... with immunoinflammatory diseases and cytokine-dependent tumours....

  19. The Norwegian immunisation register--SYSVAK.

    Science.gov (United States)

    Trogstad, L; Ung, G; Hagerup-Jenssen, M; Cappelen, I; Haugen, I L; Feiring, B

    2012-04-19

    The Norwegian immunisation register, SYSVAK, is a national electronic immunisation register. It became nationwide in 1995. The major aim was to register all vaccinations in the Childhood Immunisation Programme to ensure that all children are offered adequate vaccination according to schedule in the programme, and to secure high vaccination coverage. Notification to SYSVAK is mandatory, based on personal identification numbers. This allows follow up of individual vaccination schedules and linkage of SYSVAK data to other national health registers for information on outcome diagnoses, such as the surveillance system for communicable diseases. Information from SYSVAK is used to determine vaccine coverage in a timely manner. Coverage can be broken down to regional/local levels and used for active surveillance of vaccination coverage and decisions about interventions. During the 2009 influenza A(H1N1)pdm09 pandemic, an adaptation of SYSVAK enabled daily surveillance of vaccination coverage on national and regional levels. Currently, data from SYSVAK are used, among others, in studies on adverse events related to pandemic vaccination. Future challenges include maximising usage of collected data in surveillance and research, and continued improvement of data quality. Immunisation registers are rich sources for high quality surveillance of vaccination coverage, effectiveness, vaccine failure and adverse events, and gold mines for research.

  20. Drug Treatment Combined with BCG Vaccination Reduces Disease Reactivation in Guinea Pigs Infected with Mycobacterium tuberculosis

    Science.gov (United States)

    Shang, Shaobin; Shanley, Crystal A.; Caraway, Megan L.; Orme, Eileen A.; Henao-Tamayo, Marcela; Hascall-Dove, Laurel; Ackart, David; Orme, Ian M.; Ordway, Diane J.; Basaraba, Randall J.

    2012-01-01

    Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against M. tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease. PMID:22244979

  1. Murine immune responses to oral BCG immunization in the presence or absence of prior BCG sensitization.

    Science.gov (United States)

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2010-02-01

    Oral delivery of live Mycobacterium bovis BCG in a lipid matrix invokes cell-mediated immune (CMI) responses in mice and consequent protection against pulmonary challenge with virulent mycobacteria. To investigate the influence of prior BCG sensitization on oral vaccine efficacy, we assessed CMI responses and BCG colonization of the alimentary tract lymphatics 5 months after oral vaccination, in both previously naive mice and in mice that had been sensitized to BCG by injection 6 months previously. CMI responses did not differ significantly between mice that received subcutaneous BCG followed by oral BCG and those that received either injected or oral BCG alone. In vivo BCG colonization was predominant in the mesenteric lymph nodes after oral vaccination; this colonizing ability was not influenced by prior BCG sensitization. From this murine model study, we conclude that although prior parenteral-route BCG sensitization does not detrimentally affect BCG colonization after oral vaccination, there is no significant immune-boosting effect of the oral vaccine either.

  2. BCG induced granulomatous prostatitis ; a case report

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Min Hoan; Seong, Chang Kyu; Lee, Kyoung Ho; Kim, Seung Hyup [College of Medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of)

    2000-04-01

    Granulomatous prostatitis was relatively uncommon until the introduction of intravesical BCG for the treament of bladder cancer. Since that time, there has been an increase in the number of cases of granulomatous prostatitis, but the domestic literature contains no report. We recently encountered a classic case of BCG induced granulomatous prostatitis and describe this case, including its radiologic findings. (author)=20.

  3. Non-specific immunological effects of selected routine childhood immunisations: systematic review

    Science.gov (United States)

    Voysey, Merryn; McQuaid, Fiona; de Nie, Karlijn; Ryan, Rebecca; Orr, Olivia; Uhlig, Ulrike; Sande, Charles; O’Connor, Daniel; Pollard, Andrew J

    2016-01-01

    Objective To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus. Design Systematic review of randomised controlled trials, cohort studies, and case-control studies. Data sources Embase, PubMed, Cochrane library, and Trip searched between 1947 and January 2014. Publications submitted by a panel of experts in the specialty were also included. Eligibility criteria for selecting studies All human studies reporting non-specific immunological effects after vaccination with standard childhood immunisations. Studies using recombinant vaccines, no vaccine at all, or reporting only vaccine specific outcomes were excluded. The primary aim was to systematically identify, assemble, and review all available studies and data on the possible non-specific or heterologous immunological effects of BCG; measles; mumps, measles, and rubella (MMR); diphtheria; tetanus; and pertussis vaccines. Results The initial search yielded 11 168 references; 77 manuscripts met the inclusion criteria for data analysis. In most included studies (48%) BCG was the vaccine intervention. The final time point of outcome measurement was primarily performed (70%) between one and 12 months after vaccination. There was a high risk of bias in the included studies, with no single study rated low risk across all assessment criteria. A total of 143 different immunological variables were reported, which, in conjunction with differences in measurement units and summary statistics, created a high number of combinations thus precluding any meta-analysis. Studies that compared BCG vaccinated with unvaccinated groups showed a trend towards increased IFN-γ production in vitro in the vaccinated groups. Increases were also observed for IFN-γ measured after BCG vaccination in response to in vitro stimulation with microbial antigens from Candida albicans, tetanus toxoid, Staphylococcus aureas, lipopolysaccharide, and

  4. BCG vaccination: a role for vitamin D?

    Directory of Open Access Journals (Sweden)

    Maeve K Lalor

    Full Text Available BACKGROUND: BCG vaccination is administered in infancy in most countries with the aim of providing protection against tuberculosis. There is increasing interest in the role of vitamin D in immunity to tuberculosis. This study objective was to determine if there was an association between circulating 25(OHD concentrations and BCG vaccination status and cytokine responses following BCG vaccination in infants. METHODS: Blood samples were collected from UK infants who were vaccinated with BCG at 3 (n = 47 and 12 (n = 37 months post BCG vaccination. These two time-points are denoted as time-point 1 and time-point 2. Two blood samples were also collected from age-matched unvaccinated infants (n = 32 and 28 respectively, as a control group. Plasma vitamin D concentrations (25(OHD were measured by radio-immunoassay. The cytokine IFNγ was measured in supernatants from diluted whole blood stimulated with M.tuberculosis (M.tb PPD for 6 days. RESULTS: 58% of infants had some level of hypovitaminosis (25(OHD <30 ng/ml at time-point 1, and this increased to 97% 9 months later. BCG vaccinated infants were almost 6 times (CI: 1.8-18.6 more likely to have sufficient vitamin D concentrations than unvaccinated infants at time-point 1, and the association remained strong after controlling for season of blood collection, ethnic group and sex. Among vaccinees, there was also a strong inverse association between IFNγ response to M.tb PPD and vitamin D concentration, with infants with higher vitamin D concentrations having lower IFNγ responses. CONCLUSIONS: Vitamin D may play an immuno-regulatory role following BCG vaccination. The increased vitamin D concentrations in BCG vaccinated infants could have important implications: vitamin D may play a role in immunity induced by BCG vaccination and may contribute to non-specific effects observed following BCG vaccination.

  5. Views of Zulus and Southern Sothos on immunisation

    Directory of Open Access Journals (Sweden)

    A.J. Lubbe

    1984-09-01

    Full Text Available The promotion of good health and the prevention of disease are two of the aims of community health care that can, to a large extent be realised by means of immunisation. Immunisation does not only make it possible to control the spread of a number of infectious diseases, but also enhances the overall health status of a community.

  6. Australian immunisation registers: established foundations and opportunities for improvement.

    Science.gov (United States)

    Chin, L K; Crawford, N W; Rowles, G; Buttery, J P

    2012-04-19

    The National Immunisation Program Schedule in Australia is formulated and funded nationally under the population-wide Medicare system. The policy is implemented by the eight state and territory jurisdictions. The national immunisation registers consist of the Australian Childhood Immunisation Register (ACIR), and, more recently, the National Human Papillomavirus (HPV) Vaccination Program Register. Moreover, a variety of jurisdiction-based registers and primary care practice software systems exist, which interact with the national registers. General practitioners can obtain reports listing patients under seven years attending their practice and recorded as 'not fully immunised', and immunisation coverage rates for their practice linked to government incentives through Medicare. A 2011 report documents national coverage of 91.8% fully immunised at 12 months, and 92.6% at 24 months. The HPV register provides information on vaccination coverage with the potential to link with a register of cervical cancer screening results. Limitations of current national register include inability to easily access immunisation histories beyond seven years of age, and issues of underreporting and timeliness, which impact significantly the immunisation coverage estimates. The linkage of these registers with healthcare outcome data will further enhance public health outcomes by enabling rapid, population-level vaccine safety and effectiveness investigations in a nation with a track record as an 'early adopter' of new childhood vaccines.

  7. Mitsuda's reactions: induced by BCG in the normal Rhesus ("Macacca mulatta"

    Directory of Open Access Journals (Sweden)

    M. J. Pereira Filho

    1955-12-01

    the repetition of the tests, even though the intensity of the reaction always remains the same. This precocious reaction (Fernandez type occurs both shortly and long time after the application of the BCG. Its precocity depends not of the antigen only because the first Mitsuda's reaction after the BCG application occurs after some time and seems not influenced by the control lepromin test effected on the Rhesus before the BCG. 5 On the control group, the animals which received a.a.f. bacilli suspensions (Mycobacterium sp.; M. avium, and M. smegmatis, did not show reverseals of the Mitsuda's reaction. Two Rhesus, however, which received dead BCG (120ºC autoclave 1 hour, one intradermically (0.006 g and the other orally (1.2 g, did both present reversals of the Mitsuda's reaction, with weak positivity (+. In all animals of the control-group, the allergic reactions were found negative. 6 Strong local inflammatory reactions were observed in the Rhesus that had received living BCG by intradermal via, and in the one submitted to multipunctures, there occurred the formation of a large caseous abcess. 7 The allergic tuberculinic and infratuberculinic reactions appeared dissociated from the Mitsuda's reactions: sometimes they are more precocious, occurring before of the lepromin test; on other occasions they disappear, when the Mitsuda's reactions still persist; and finally, they may be absent, when the latter occur, especially after the oral application of the BCG. 8 In Rhesus which received BCG by testicular and peritonela via, in the infratuberculinic test (0.1 ml of total BCG extract, besides the classic answer, which occurs between 48 and 96 hours, one could observe a delayed answer (15 to 20 days, represented by a non-erythematous nodule, which persists for 11-14 days.

  8. Nonclinical Development of BCG Replacement Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Bernd Eisele

    2013-04-01

    Full Text Available The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  9. Lupus vulgaris at the site of BCG vaccination: report of three cases.

    Science.gov (United States)

    Farsinejad, K; Daneshpazhooh, M; Sairafi, H; Barzegar, M; Mortazavizadeh, M

    2009-07-01

    Lupus vulgaris (LV) is a rare complication of the bacille Calmette-Guérin (BCG) vaccination, and about 65 cases of inoculation tuberculosis resembling LV have been reported in the literature. We report three cases of LV, developing many years later at the inoculation site of BCG vaccine. All three cases had a single BCG vaccination, with a LV lesion at or in the vicinity of the vaccination site, a strong positive Mantoux test, noncaseating granuloma histologically, and two of the patients had a positive PCR result for mycobacterial complex. One of the patients had an unusually delayed appearance of the LV lesion, after an interval of about 17 years, and another case was remarkable because of the large size of the lesion (210 x 110 mm).

  10. Bladder Cancer Immunotherapy: BCG and Beyond

    Directory of Open Access Journals (Sweden)

    Eric J. Askeland

    2012-01-01

    Full Text Available Mycobacterium bovis bacillus Calmette-Guérin (BCG has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1 immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10.

  11. Bladder Cancer Immunotherapy: BCG and Beyond.

    Science.gov (United States)

    Askeland, Eric J; Newton, Mark R; O'Donnell, Michael A; Luo, Yi

    2012-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1) immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10.

  12. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, Allan Randrup;

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...... with IL-1alpha coupled to purified protein derivative of tuberculin (PPD). Both unprimed and primed animals developed IgG aAb to IL-1alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1beta. The induced anti-IL-1alpha aAb inhibited binding...

  13. [Assessment of BCG vaccine practices].

    Science.gov (United States)

    Lechiche, C; Charpille, M; Saissi, G; Sotto, A

    2016-01-01

    Tuberculosis is a major public health problem. In France, the vaccine against tuberculosis (Bacillus Calmette-Guerin, BCG) is in decline. This decline is firstly due to changes in BGG administration that were implemented in 2006 and secondly because of new recommandations in 2007 that ended compulsory vaccination. To determine their position on this vaccine, in 2013-2014 we asked general practitioners, pediatricians, and Maternal and Infantile Protection Center physicians in the Gard and Herault departments (in Southern France) why this vaccine was not administered and their suggestions for improvement. Most of these doctors (73.9%) stated that they did not oppose this vaccination for children. They expressed concern about potential side effects, technical problems (intradermic injection, multi-dose bottles) and parents' refusal. One quarter of these physicians would have preferred that this vaccine remains compulsory and one third that this vaccine be administered in the maternity hospital. They also requested simplified criteria for patient eligibility, technical improvements (training for intradermal injection, single-dose vaccine) and more information for the public concerning this vaccination.

  14. BCG skin reaction in Mantoux-negative healthy children

    Directory of Open Access Journals (Sweden)

    Sodhi Sukhbir

    2005-03-01

    Full Text Available Abstract Background Tuberculosis poses a great challenge, especially in children. The response of BCG Test may be different in previously vaccinated children and needs to be considered before interpreting positivity for TB. This study has been carried out to determine the pattern of BCG reaction comparing previously vaccinated with non-vaccinated children. Methods The study was conducted in the healthy school children aged 4–6 years. The BCG skin reaction in Mantoux-negative children was compared between children with and without previous BCG scar. After the Mantoux and BCG Test, the analysis of variance was done as per protocol. Results Out of 50 children previously BCG vaccinated, 39(78% showed exaggerated BCG test responses while out of another 50 children who were not vaccinated for TB, only 9(18% showed exaggerated BCG Test response (p-value Conclusion The present study indicates that normal healthy children may have a mild exaggerated BCG Test response i.e. induration up to 8 mm because of prior BCG vaccination. Therefore, BCG Test, though important should not be the only criteria for start of chemotherapy for TB in children as the side effects of drugs may cause much morbidity. An induration up to 8 mm after the BCG Test can be normal in Indian settings due to exposure to Mycobacterium in environment and/or BCG vaccine.

  15. Financial requirements of immunisation programmes in developing countries: a 2004-2014 perspective.

    Science.gov (United States)

    Peny, Jean-Michel; Gleizes, Olivier; Covilard, Jean-Pierre

    2005-08-31

    to all relevant developing countries as soon as they are available, funding requirements to cover the associated total costs over the 10-year period were estimated to be about US$ 30 billion. Vaccines-related costs represent the largest share, with estimated costs of US$ 21 billion (among which 18 billion for new vaccines), the remaining needs being split between capital costs and other recurrent costs. Accounting for the main imponderables (such as delay in vaccines launch compared to industry plans) as well as probable phasing of vaccine introduction in countries, the total costs of immunisation would be reduced to US$ 14-17 billion over the same period. Vaccines-related costs represent the largest share (US$ 7.1-9.3 billion, among which 4.3-6.5 billion for new vaccines). This study advocates for the anticipation of the substantial financial resources needed to (a) purchase and introduce these vaccines in the developing countries in order to reduce the time lag between availability in industrialised and developing countries; and (b) stimulate vaccine researchers and manufacturers to continue research and development of much needed vaccines for the developing world.

  16. Effectiveness of BCG vaccination to aged mice

    Directory of Open Access Journals (Sweden)

    Ito Tsukasa

    2010-09-01

    Full Text Available Abstract Background The tuberculosis (TB still increases in the number of new cases, which is estimated to approach 10 million in 2010. The number of aged people has been growing all over the world. Ageing is one of risk factors in tuberculosis because of decreased immune responses in aged people. Mycobacterium bovis Bacillus Calmette Guérin (BCG is a sole vaccine currently used for TB, however, the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug resistant Mycobacterium tuberculosis (MDR-TB make us to see the importance of vaccination against TB in new light. In this study, we evaluated the efficacy of BCG vaccination in aged mice. Results The Th1 responses, interferon-γ production and interleukin 2, in BCG inoculated aged mice (24-month-old were comparable to those of young mice (4- to 6-week-old. The protection activity of BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as young mice. Conclusion These findings suggest that vaccination in aged generation is still effective for protection against tuberculosis.

  17. Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur

    Directory of Open Access Journals (Sweden)

    Degrave Wim M

    2011-04-01

    Full Text Available Abstract Background Bacille Calmette-Guerin (BCG is currently the only available vaccine against tuberculosis (TB and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. Results The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa, Rv1926c (BCG1965c, Mpb63 and Rv1886c (BCG1923c, Ag85B in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2 and Rv0350 (BCG0389, DnaK, show the opposite pattern. Conclusions Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.

  18. Non-specific immunity of BCG vaccine: A perspective of BCG immunotherapy

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    Najeeha Talat Iqbal

    2014-01-01

    Full Text Available BCG is a widely used vaccine worldwide for neonates including Pakistan. BCG has more than 90% coverage through the EPI program which was introduced in 1965 in Pakistan. BCG has limited efficacy against the transmissible form of pulmonary tuberculosis in high TB endemic countries. However, BCG vaccination continues in these countries because BCG confers protection against the disseminated form of TB in children. BCG has also shown some protection against leprosy and certain forms of cancers. One reason for such nonspecific protection may be that BCG activates APCs via PAMPS that interacts with TLRs (2, 4 & 8, which initiate the inflammatory cascade thereby recruiting inflammatory cells to the site of infection and providing maturation signals for neutrophils, macrophages and dendritic cells. Such activation may be crucial for restricting the infection at the initial site. Furthermore, activation of the pro-inflammatory cascade also results in expression of adhesion molecules, co-stimulatory molecules as well as MHC class II molecule. MHC class II molecules engage CD4+ cells via the TCR receptor while the adhesion and costimulatory molecules bind to their respective receptors on CD4+ T cells for additional high affinity binding for T cell activation. Although activation of the innate arm may not provide subsequent memory, activation of T cells may introduce a certain level of memory response and therefore, may form a rational basis for BCG immunotherapy. This review, therefore, focuses on the immune activation related to both the innate and adaptive arm of the immune response that has been reported and further explores the utility of BCG immunotherapy related to non TB conditions.

  19. BCG protects toddlers during a tuberculosis outbreak.

    LENUS (Irish Health Repository)

    Gaensbauer, J T

    2009-05-01

    In 2007, an outbreak of tuberculosis occurred in a toddler population attending two child care centres in Cork, Ireland. Of 268 children exposed, 18 were eventually diagnosed with active tuberculosis. We present the initial clinical and radiographic characteristics of the active disease group. Mantoux testing was positive in only 66% of cases. All cases were either pulmonary or involved hilar adenopathy on chest radiograph; there were no cases of disseminated disease or meningitis. 24% of the exposed children had been previously vaccinated with BCG, and no case of active disease was found in this group (p = 0.016), suggesting a profound protective effect of BCG in this population. Our experience provides evidence supporting a protective effect of BCG against pulmonary disease in young children.

  20. BCG protects against tuberculosis irrespective of HIV status

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, Daniel; Range, Nyagosya; PrayGod, George

    2013-01-01

    While BCG vaccine protects against severe tuberculosis (TB) in children, its effect against adult TB is questionable. Furthermore, it is not known if HIV co-infection modifies the effect of BCG. Among 352 pairs of Tanzanian TB cases and matched controls, the BCG scar was associated with a reduced...

  1. DNA immunisation. New histochemical and morphometric data

    Directory of Open Access Journals (Sweden)

    D Ehirchiou

    2010-01-01

    Full Text Available Splenic germinal center reactions were measured during primary response to a plasmidic DNA intramuscular injection. Cardiotoxin-pretreated Balb/c mice were immunized with DNA plasmids encoding or not the SAG1 protein, a membrane antigen of Toxoplasma gondii. Specific anti-SAG1 antibodies were detected on days 16 and 36 after injection of coding plasmids. The results of ELISAs showed that the SAG1-specific antibodies are of the IgG2a class. Morphometric analyses were done on serial immunostained cryosections of spleen and draining or non-draining lymph nodes. This new approach made it possible to evaluate the chronological changes induced by DNA immunisation in the germinal centres (in number and in size. Significant increases in the number of germinal centres were measured in the spleen and only in draining lymph nodes after plasmid injection. the measured changes of the germinal centers appeared to result from the adjuvant stimulatory effect of the plasmidic DNA since both the coding and the noncoding plasmid DNA induced them. No measurable changes were recorded in the Tdependent zone of lymph organs.

  2. The role of the Immunisation Adverse Events Clinic at The Children's Hospital at Westmead.

    Science.gov (United States)

    Wood, Nicholas J

    2010-01-01

    Specialist immunisation clinics review and manage children who have experienced an adverse event following immunisation and provide advice to parents and health care providers regarding the revaccination of these children. Information collected by these clinics supplement passive surveillance data and allow the investigation of suspected safety signals associated with the delivery of immunisation programs. This paper reviews the role and experience of the Immunisation Adverse Events Clinic at The Children's Hospital at Westmead and identifies areas for development.

  3. Compliance with diphtheria, tetanus, and pertussis immunisation in Bangladesh

    DEFF Research Database (Denmark)

    Zeitlyn, S; Rahman, A K; Nielsen, B H;

    1992-01-01

    associated with mothers' failure to comply with the second dose were lack of education and low income. Children whose mothers knew most about immunisation at first interview were more likely to have their second dose. CONCLUSIONS: Preventive health care services such as immunisation are appropriately offered...... in treatment centres, but compliance among children varies with socioeconomic status and mother's education. Further research should be aimed at ways to make health education more effective among uneducated parents.......OBJECTIVE: To evaluate factors associated with non-compliance with having second vaccination against diphtheria, tetanus, and pertussis in a treatment centre in Dhaka to determine which children were most at risk of not completing immunisation. DESIGN: Cohort study of infants given first dose...

  4. Vaccination for tomorrow: the need to improve immunisation rates.

    Science.gov (United States)

    Kassianos, George

    2010-01-01

    Since the 1998 health scare about measles mumps and rubella (MMR) immunisation, vaccination rates for measles have suffered. Although these recovered for a brief period in 2004-05, they have stalled again and latest figures suggest that only 85% of children are now immunised against this disease. The UK has become one of the five countries in the European Union with the highest measles rates. Meanwhile the wider picture indicates that other vaccination rates, including for seasonal influenza, are not meeting targets. This is a potential sign that the MMR scare and myths around immunisation are setting a worrying trend of some people losing confidence in the practice of vaccination. The UK has expanded its childhood immunisation programme to include the human papilloma virus vaccine (HPV) which protects against some types of cervical cancer. New life-saving vaccines for diseases, including meningococcal B meningitis (a strain of meningitis not yet covered by the existing vaccination programme), shingles and hepatitis C will soon become available. It is therefore important that information is available to the general public about the excellent safety record and benefits of vaccination to ensure that as many people as possible can take advantage of these new vaccines. This article explores the current uptake of, and attitudes towards, vaccination programmes and discusses some myths about immunisation. It suggests that community health care teams with access to adults, including parents of children and young people who need vaccination, are well placed to help challenge some of these myths and promote the benefits of immunisation. Practical suggestions are included on how this can be achieved.

  5. A family history of serious complications due to BCG vaccination is a tool for the early diagnosis of severe primary immunodeficiency.

    Science.gov (United States)

    Roxo-Junior, Pérsio; Silva, Jorgete; Andrea, Mauro; Oliveira, Larissa; Ramalho, Fernando; Bezerra, Thiago; Nunes, Altacílio A

    2013-09-10

    Severe Combined Immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency (PID). Complications of BCG vaccination, especially disseminated infection and its most severe forms, are known to occur in immunodeficient patients, particularly in SCID. A carefully taken family history before BCG injection as well as delaying vaccination if PID is suspected could be a simple and effective method to avoid inappropriate vaccination of an immunodeficient child in some cases until the prospect of newborn screening for SCID has been fully developed. We describe a patient with a very early diagnosis of SCID, which was suspected on the basis of the previous death of two siblings younger than one year due to severe complications secondary to the BCG vaccine. We suggest that a family history of severe or fatal reactions to BCG should be included as a warning sign for an early diagnosis of SCID.

  6. Descendant of daughter Brazilian BCG Moreau substrain in Poland.

    Science.gov (United States)

    Krysztopa-Grzybowska, Katarzyna; Brzezińska, Sylwia; Augustynowicz-Kopeć, Ewa; Polak, Maciej; Augustynowicz, Ewa; Lutyńska, Anna

    2012-08-10

    In this study we assessed the genomic stability of Mycobacterium bovis BCG Moreau seed lots used in Poland for BCG vaccine production since 1955 by pulsed field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP) and random amplification of polymorphic DNA (RAPD). BCG vaccine lots were more closely related the original lot -M. bovis BCG Rio de Janeiro Moreau compared with seeds used before 1980, which is consistent with seed lot distribution recorded in the archives. We confirmed the presence of RD8, RD2, senX3-regX3, RD14, DU2-I, whiB3, trcR, the second copy of IS6110 inserted in the promoter region of phoP, mutation D322G in phoR, ΔRD1, and ΔfadD26-ppsA in M. bovis BCG Moreau used for BCG production in Poland. However, unlike the Rio de Janeiro parent BCG, the BCG Moreau substrain used in Poland does not harbour a deletion in Rv3887c, a region that is involved in the membrane transport protein that is part of the ESX-2 type VII secretion system. Differences in the distribution of BCG Moreau for its subsequent use for manufacturing influenced the microevolution of BCG Moreau used in Brazil and Poland.

  7. The National Immunisation Programme in the Netherlands. Developments in 2006

    NARCIS (Netherlands)

    Abbink F; Avoort HGAM van der; Berbers WAM; Binnendijk RS van; Boot HJ; Duynhoven YTHP van; Geraedts JLE; Gerritsen AAM; Greeff SC de; Hofhuis A; Hahne SJM; Kemmeren JM; Kimman TG; Klein MR; Koedijk FDH; Koopmans MPG; Kremer K; Maas NAT van der; Mangen MJJ; Meijer A; Mooi FR; Mylius SD; Notermans DW; Op de Coul ELM; Sande MAB van der; Schouls LM; Soolingen D van; Steenbergen JE van; Vermeer-de Bondt PE; Wallinga J; Wit GA de; Melker HE de; Gerritsen AAM; Hahne SJM; EPI

    2007-01-01

    In 2006 several changes were made in the Dutch National Immunisation Programme (NIP): Hepatitis B vaccination at birth was added for children born to mothers positive for hepatitis B surface antigen; a new vaccine for diphtheria, tetanus, pertussis (a-cellular), poliomyelitis and Haemophilus influen

  8. Injection safety for immunisation--Andhra Pradesh experience.

    Science.gov (United States)

    Kaipilyawar, Satish B; Rao, R Gopal Krishna

    2005-04-01

    Injection safety is one component of a major immunisation project being implemented in partnership with Government of Andhra Pradesh and PATH, an international NGO. Prior to the project wrong and dangerous injection giving practices were present among the staff which needed immediate attention. It was decided to introduce auto disable syringes along with safety boxes with high quality training to staff and make all these available to all districts along with hepatitis B introduction in the routine immunisation. The State of Andhra Pradesh became the first to implement 'bundling' concept in the immunisation project. Implementation was planned to be done in a phased manner to cover all the 23 districts over a five-year period. For routine immunisation sessions, smaller locally produced boxes may be more acceptable. The Government of India made a decision on 21st July, 2004 on implementing injection safety. Injection safety and proper disposal of used needles and syringes can be successfully advocated if medical associations, paediatric associations, key governmental bodies and international agencies come together. PATH established a group and holds the secretariat for the India injection safety coalition on similar basis as the Safe Injection Global Network of WHO (SIGN). Description of AP system for safe disposal of needles and syringes using manual needle-cutters and plastics recycling has been depicted in this article.

  9. Has decentralisation affected child immunisation status in Indonesia?

    Directory of Open Access Journals (Sweden)

    Asri Maharani

    2014-08-01

    Full Text Available Background: The past two decades have seen many countries, including a number in Southeast Asia, decentralising their health system with the expectation that this reform will improve their citizens’ health. However, the consequences of this reform remain largely unknown. Objective: This study analyses the effects of fiscal decentralisation on child immunisation status in Indonesia. Design: We used multilevel logistic regression analysis to estimate these effects, and multilevel multiple imputation to manage missing data. The 2011 publication of Indonesia's national socio-economic survey (Susenas is the source of household data, while the Podes village census survey from the same year provides village-level data. We supplement these with local government fiscal data from the Ministry of Finance. Results: The findings show that decentralising the fiscal allocation of responsibilities to local governments has a lack of association with child immunisation status and the results are robust. The results also suggest that increasing the number of village health centres (posyandu per 1,000 population improves probability of children to receive full immunisation significantly, while increasing that of hospitals and health centres (puskesmas has no significant effect. Conclusion: These findings suggest that merely decentralising the health system does not guarantee improvement in a country's immunisation coverage. Any successful decentralisation demands good capacity and capability of local governments.

  10. Immunisation registers in Italy: a patchwork of computerisation.

    Science.gov (United States)

    Alfonsi, V; D'Ancona, F; Rota, M C; Giambi, C; Ranghiasci, A; Iannazzo, S

    2012-04-26

    In Italy, the 21 regional health authorities are in charge of organising and implementing their own vaccination strategy, based on the national vaccine plan. Immunisation coverage varies greatly among the regions for certain vaccines. Efforts to increase childhood immunisation coverage have included initiatives to develop and implement computerised immunisation registers in as many regions as possible. We undertook a cross-sectional online survey in July 2011 to provide an updated picture of the use, heterogeneity and main functions of different computerised immunisation registers used in the Italian regions and to understand the flow of information from local health units to the regional authorities and to the Ministry of Health. Comparing current data with those obtained in 2007, a substantial improvement is evident. A total of 15 regions are fully computerised (previously nine), with 83% of local health units equipped with a computerised register (previously 70%). Eight of the 15 fully computerised regions use the same software, simplifying data sharing. Only four regions are able to obtain data in real time from local health units. Despite the progress made, the capacity to monitor vaccination coverage and to exchange data appears still limited.

  11. Feasibilty of oral immunisation with LTB-based edible vaccines

    NARCIS (Netherlands)

    Lauterslager, Tosca Genevieve Maria

    2003-01-01

    This thesis describes the research to explore the feasibility of plants for oral vaccination. The research focussed on a model of LTB produced in potato tubers or ovalbumin (OVA) as antigen and tested in mice. A general introduction into the backgrounds of oral immunisation is given in Chapter 1. Th

  12. Osteíte por BCG

    OpenAIRE

    Yamada,André Fukunishi; Pellegrini,Juliana Barbosa; Cunha,Luciana Menezes; Fernandes, Artur da Rocha Corrêa

    2009-01-01

    Os autores relatam o caso de um menino de 1 ano e 9 meses que apresentou lesão osteolítica na região proximal do úmero direito. Com base na história clínica e em achados histológicos, os autores suspeitaram de osteíte pósvacina BCG. Após o início do tratamento antituberculose, os sintomas desapareceram e o paciente apresentou melhora radiológica. Os autores descrevem esta entidade incomum na prática pediátrica e alertam para possíveis complicações da vacina BCG.

  13. Præventis, the immunisation register of the Netherlands: a tool to evaluate the National Immunisation Programme.

    Science.gov (United States)

    van Lier, A; Oomen, P; de Hoogh, P; Drijfhout, I; Elsinghorst, B; Kemmeren, J; Conyn-van Spaendonck, M; de Melker, H

    2012-04-26

    Vaccination coverage is an important performance indicator of any national immunisation programme (NIP). To monitor the vaccination coverage in the Netherlands, an electronic national immunisation register called ‘Præventis’ was implemented in 2005. Præventis has a link with the population register and can produce letters of invitation for the NIP, register and validate administered vaccinations. The database is used to monitor the vaccination process, produce reminder letters, control the stock of vaccines and provides information used for paying the fees to the different executive organisations involved. Præventis provides a crucial tool for the evaluation of the NIP by producing (sub)national vaccination coverage estimates with high accuracy and allowing additional research: identifying populations at high risk for low coverage based on existing data, conducting specific studies where individuals included in the immunisation register are approached for further research, using vaccination coverage data for the interpretation of (sero)surveillance data, and linking the immunisation register with disease registers to address vaccine safety or vaccine effectiveness. The ability to combine Præventis data with data from other databases or disease registers and the ability to approach individuals with additional research questions offers opportunities to identify areas of priority for improving the Dutch NIP.

  14. Cellular immunity confers transient protection in experimental Buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination.

    Directory of Open Access Journals (Sweden)

    Alexandra G Fraga

    Full Text Available BACKGROUND: Buruli ulcer (BU is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better preventive strategy. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the mouse model to characterize the histological and cytokine profiles triggered by vaccination with either BCG or mycolactone-negative M. ulcerans, followed by footpad infection with virulent M. ulcerans. We observed that BCG vaccination significantly delayed the onset of M. ulcerans growth and footpad swelling through the induction of an earlier and sustained IFN-γ T cell response in the draining lymph node (DLN. BCG vaccination also resulted in cell-mediated immunity (CMI in M. ulcerans-infected footpads, given the predominance of a chronic mononuclear infiltrate positive for iNOS, as well as increased and sustained levels of IFN-γ and TNF. No significant IL-4, IL-17 or IL-10 responses were detected in the footpad or the DLN, in either infected or vaccinated mice. Despite this protective Th1 response, BCG vaccination did not avoid the later progression of M. ulcerans infection, regardless of challenge dose. Immunization with mycolactone-deficient M. ulcerans also significantly delayed the progression of footpad infection, swelling and ulceration, but ultimately M. ulcerans pathogenic mechanisms prevailed. CONCLUSIONS/SIGNIFICANCE: The delay in the emergence of pathology observed in vaccinated mice emphasizes the relevance of protective Th1 recall responses against M. ulcerans. In future studies it will be important to determine how the transient CMI induced by vaccination is compromised.

  15. Arthritis and iritis after BCG therapy for bladder cancer.

    Science.gov (United States)

    Price, G E

    1994-03-01

    A patient with preexisting inactive ankylosing spondylitis experienced a recurrence of back pain and his first episode of acute peripheral arthritis and iritis after a second course of treatment with BCG for bladder cancer. The occurrence of iritis after BCG therapy has not been reported. The recurrence of spondyloarthropathy and the new appearance of iritis may have been part of a generalized enhancement of immunological reactivity produced by the BCG.

  16. CLINICAL MANAGEMENT OF LOCALIZED BCG ADVERSE EVENTS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Thais das Neves Fraga MOREIRA

    Full Text Available SUMMARY BCG adverse events (BCG-AE are rare conditions with no well-established treatment. This study aims to describe clinical characteristics and outcome of localized BCG-AE. Children with BCG-AEs who were treated at the Reference Center for Special Immunobiologicals of the Federal University of São Paulo from 2009 to 2011 were included. Patients were followed monthly until 3 months after healing. One hundred and twenty-seven patients with localized BCG-AE were followed: 67 (52.7% had suppurative lymphadenitis; 30 (23.6% injection-site abscess; five (3.9% had enlarged lymph node > 3 cm; four (3.1% had ulcer > 1 cm; and one (0.8% had a local bacterial infection. Five patients (3.9% had more than one BCG-AE simultaneously. Fifteen patients (11.8% had atypical manifestations: seven wart-like lesions; five BCG reactivations; two other dermatologic lesions and one with vasomotor phenomenon. Isoniazid was used in 96 patients with typical BCG-AE (85.7% until lesion resolution which took place 3.1 months later (in median; the healing rate was 90.6%. Patients with atypical manifestations had an individual approach. Regarding the outcome, 105/112 patients with typical AE and 13/15 patients with atypical AE had resolution of BCG-AE. Localized BCG-AE caused by BCG Moreau RJ had positive outcome when treated with a short course of isoniazid. Atypical BCG-AE are not infrequent.

  17. Genome sequencing and analysis of BCG vaccine strains.

    Directory of Open Access Journals (Sweden)

    Wen Zhang

    Full Text Available BACKGROUND: Although the Bacillus Calmette-Guérin (BCG vaccine against tuberculosis (TB has been available for more than 75 years, one third of the world's population is still infected with Mycobacterium tuberculosis and approximately 2 million people die of TB every year. To reduce this immense TB burden, a clearer understanding of the functional genes underlying the action of BCG and the development of new vaccines are urgently needed. METHODS AND FINDINGS: Comparative genomic analysis of 19 M. tuberculosis complex strains showed that BCG strains underwent repeated human manipulation, had higher region of deletion rates than those of natural M. tuberculosis strains, and lost several essential components such as T-cell epitopes. A total of 188 BCG strain T-cell epitopes were lost to various degrees. The non-virulent BCG Tokyo strain, which has the largest number of T-cell epitopes (359, lost 124. Here we propose that BCG strain protection variability results from different epitopes. This study is the first to present BCG as a model organism for genetics research. BCG strains have a very well-documented history and now detailed genome information. Genome comparison revealed the selection process of BCG strains under human manipulation (1908-1966. CONCLUSIONS: Our results revealed the cause of BCG vaccine strain protection variability at the genome level and supported the hypothesis that the restoration of lost BCG Tokyo epitopes is a useful future vaccine development strategy. Furthermore, these detailed BCG vaccine genome investigation results will be useful in microbial genetics, microbial engineering and other research fields.

  18. Tuberculin reaction, BCG scar, and lower female mortality

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik;

    2006-01-01

    Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar in respo......Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar...

  19. [Immunisation schedule of the Spanish Association of Paediatrics: 2013 recommendations].

    Science.gov (United States)

    Moreno-Pérez, D; Álvarez García, F J; Arístegui Fernández, J; Barrio Corrales, F; Cilleruelo Ortega, M J; Corretger Rauet, J M; González-Hachero, J; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

    2013-01-01

    The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on the safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded as routine vaccinations those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in situations of risk. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Nevertheless, the achievement of a unified immunisation schedule in all regions of Spain is a top priority for the CAV-AEP. Based on the latest epidemiological trends, CAV-AEP follows the innovations proposed in the last year's schedule, such as the administration of the first dose of the MMR and the varicella vaccines at age 12 months and the second dose at age 2-3 years, as well as the administration of the Tdap vaccine at age 4-6 years, always followed by another dose at 11-14 years of age, preferably at 11-12 years. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-14 years, preferably at 11-12 years, must increase. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. Universal vaccination against varicella in the second year of life is an effective strategy and therefore a desirable objective. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. Finally, it

  20. BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Sofia Fernanda Gonçalves Zorzella-Pezavento

    2013-01-01

    Full Text Available A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65 after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

  1. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review

    Science.gov (United States)

    Soares-Weiser, Karla; López-López, José A; Kakourou, Artemisia; Chaplin, Katherine; Christensen, Hannah; Martin, Natasha K; Sterne, Jonathan A C; Reingold, Arthur L

    2016-01-01

    , assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. Conclusions Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences. PMID:27737834

  2. Invitro immune responses in children following BCG vaccination

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi V

    2006-01-01

    Full Text Available Introduction: There is still no consensus on the efficacy of BCG vaccine in the prevention of tuberculosis. This study therefore addressed the question of the magnitude of immunity afforded by BCG, by studying the effector mechanisms of protection in children. The main objectives were to assess the degree of immunity conferred by BCG vaccine in children and to identify the most immunogenic antigen(s of BCG by conducting in-vitro studies. Materials and methods: Children in the age-group of 1 to 10 years, were categorized: (A normal, and vaccinated with BCG during the first year, n=45, (B normal, without scar and with no evident history of vaccination, n=31: and (C children admitted in the hospital with a confirmed diagnosis of tuberculosis, n=31. Fractions of BCG were obtained by lysis, sonication, separation by gel chromatography, HPLC and confirmed by SDS-PAGE. In lymphoproliferative assays PBMC were cultured and stimulated with either Concanavalin-A or Tuberculin or the fractions of BCG. Stimulation indices (SI in lymphoproliferation, CD4/CD8 cells, levels of Interferon-γ (IFN- γ in the culture supernatants were measured by ELISA. Results: The vaccinated children displayed significantly high (P< 0.05 mean values of SI in LTT, CD4/CD8 cell ratio against the unfractionated, 67kDa fraction and BCG-CF Ags. While 100% of the vaccinated children had positive lymphoproliferation indices to BCG-CF, only 8.3% of the unvaccinated children were positive. Conclusion: Some of the components of BCG induced a strong Thl cell response in children. These immunogenic antigens were present in the whole cell lysate. The use of BCG vaccine for tuberculosis is worthwhile till a new vaccine is developed.

  3. TO ESTIMATE SERUM ADA LEVELS IN BCG VACCINATED CHILDREN

    Directory of Open Access Journals (Sweden)

    Manjunatha Babu

    2015-04-01

    Full Text Available BACKGROUND: Tuberculosis is an important cause of morbidity and mortality in both adults and children, especially in developing countries. For prevention of childhood tuberculosis, BCG vaccination is advocated. Protection is attained 4 - 6 weeks after BCG vaccination a nd is mainly due to cell mediated immunity. After BCG vaccination almost 12 to 15% of neonates do not develop scar but have positive cell mediated immune response. ADA estimation is simple and inexpensive method to assess the cell mediated immunity. OBJECT IVE: To estimate serum ADA levels in children with and without BCG scar, after receiving BCG vaccination. MATERIAL AND METHODS: This prospective observational study was conducted at a tertiary care hospital for a period of 2 years. Babies in post natal ward and infants up to the age of 12 weeks attending well baby clinic for BCG vaccination were included in the study. Serum ADA lev els were estimated before BCG vaccination and 12 - 14 weeks after the vaccination. ADA levels were estimated by colorimetric method. Presence or absence of BCG scar was noted at 12 - 14 weeks of age. RESULTS: A total of 75 babies followed up, of which only 60 babies noted to have scar and in rest 15 babies there was no scar noticed. Twenty unvaccinated babies at 12 weeks of age were included as controls. The Mean ADA levels are significantly elevated after BCG vaccination (34 . 12 ± 3 . 28 U/L in comparison to le vels before vaccination (12 . 55± 2 . 64 U/L with p value 0. 06. CONCLUSION: After BCG vaccination, there is increase in serum ADA levels indicating adequ ate immunity. Increase in ADA levels in children without scar after BCG vaccination may indicate the probability of adequate immunity.

  4. African horse sickness in naturally infected, immunised horses.

    Science.gov (United States)

    Weyer, C T; Quan, M; Joone, C; Lourens, C W; MacLachlan, N J; Guthrie, A J

    2013-01-01

    To determine whether subclinical cases, together with clinical cases, of African horse sickness (AHS) occur in immunised horses in field conditions, whole blood samples were collected and rectal temperatures recorded weekly from 50 Nooitgedacht ponies resident in open camps at the Faculty of Veterinary Science, University of Pretoria, Onderstepoort, during 2008-2010. The samples were tested for the presence of African horse sickness virus (AHSV) RNA by a recently developed real-time RT-PCR. It was shown that 16% of immunised horses in an AHS endemic area were infected with AHSV over a 2 year period, with half of these (8%) being subclinically infected. The potential impact of such cases on the epidemiology of AHS warrants further investigation.

  5. [Immunisation schedule of the Spanish Association of Paediatrics: 2016 recommendations].

    Science.gov (United States)

    Moreno-Pérez, D; Álvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa del Castillo, L; Ruiz-Contreras, J

    2016-01-01

    The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) annually publishes the immunisation schedule which, in our opinion, estimates optimal for children resident in Spain, considering available evidence on current vaccines. We acknowledge the effort of the Ministry of Health during the last year in order to optimize the funded unified Spanish vaccination schedule, with the recent inclusion of pneumococcal and varicella vaccination in early infancy. Regarding the funded vaccines included in the official unified immunization schedule, taking into account available data, CAV-AEP recommends 2+1 strategy (2, 4 and 12 months) with hexavalent (DTPa-IPV-Hib-HB) vaccines and 13-valent pneumococcal conjugate vaccine. Administration of Tdap and poliomyelitis booster dose at the age of 6 is recommended, as well as Tdap vaccine for adolescents and pregnant women, between 27-36 weeks gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). Coverage of human papillomavirus vaccination in girls aged 11-12 with a two dose scheme (0, 6 months) should be improved. Information for male adolescents about potential beneficial effects of this immunisation should be provided as well. Regarding recommended unfunded immunisations, CAV-AEP recommends the administration of meningococcal B vaccine, due to the current availability in Spanish communitary pharmacies, with a 3+1 scheme (3, 5, 7 and 13-15 months). CAV-AEP requests the incorporation of this vaccine in the funded unified schedule. Vaccination against rotavirus is recommended in all infants. Annual influenza immunisation and vaccination against hepatitis A are indicated in population groups considered at risk.

  6. Japan's immunisation policy in routine, pandemic and post-tsunami situations.

    Science.gov (United States)

    Murashige, N

    2011-11-01

    Immunisation is an important tool to protect individual and public health both in routine universal coverage and in complex emergency situations. Japan legally supports routine childhood immunisation against only eight diseases and recently experienced pandemic influenza and devastating earthquake and tsunami. This perspective aims to describe the current issues on Japan's immunisation policy in routine, pandemic and post-tsunami situations and to suggest solutions for them.

  7. BCG vaccination at birth and early childhood hospitalization

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Sørup, Signe; Aaby, Peter

    2017-01-01

    vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. METHODS: Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age......-protocol analyses. RESULTS: 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child......BACKGROUND: The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG...

  8. Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer.

    Directory of Open Access Journals (Sweden)

    Kathrin Buffen

    2014-10-01

    Full Text Available The anti-tuberculosis-vaccine Bacillus Calmette-Guérin (BCG is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens. It has been recently proposed that the non-specific effects of BCG are mediated through epigenetic reprogramming of monocytes, a process called trained immunity. In the present study we demonstrate that autophagy contributes to trained immunity induced by BCG. Pharmacologic inhibition of autophagy blocked trained immunity induced in vitro by stimuli such as β-glucans or BCG. Single nucleotide polymorphisms (SNPs in the autophagy genes ATG2B (rs3759601 and ATG5 (rs2245214 influenced both the in vitro and in vivo training effect of BCG upon restimulation with unrelated bacterial or fungal stimuli. Furthermore, pharmacologic or genetic inhibition of autophagy blocked epigenetic reprogramming of monocytes at the level of H3K4 trimethylation. Finally, we demonstrate that rs3759601 in ATG2B correlates with progression and recurrence of bladder cancer after BCG intravesical instillation therapy. These findings identify a key role of autophagy for the nonspecific protective effects of BCG.

  9. Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer

    NARCIS (Netherlands)

    Buffen, Kathrin; Oosting, Marije; Quintin, Jessica; Ng, Aylwin; Kleinnijenhuis, Johanneke; Magadi Gopalaiah, Vinod Kumar; van de Vosse, Esther; Wijmenga, Cisca; van Crevel, Reinout; Oosterwijk, Egbert; Grotenhuis, Anne J.; Vermeulen, Sita H.; Kiemeney, Lambertus A.; van de Veerdonk, Frank L.; Chamilos, Georgios; Xavier, Ramnik J.; van der Meer, Jos W. M.; Netea, Mihai G.; Joosten, Leo A. B.

    2014-01-01

    The anti-tuberculosis-vaccine Bacillus Calmette-Guerin (BCG) is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens

  10. [Immunisation schedule of the Spanish Association of Paediatrics: 2014 recommendations].

    Science.gov (United States)

    Moreno-Pérez, D; Alvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

    2014-01-01

    The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded, as routine vaccinations, those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in special situations. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Based on the latest epidemiological trends, CAV-AEP recommends the administration of the first dose of MMR and varicella vaccines at age 12 months, with the second dose at age 2-3 years; the administration of DTaP or Tdap vaccine at age 4-6 years, always followed by another Tdap dose at 11-12 years; and the three meningococcal C scheme at 2 months, 12 months and 12 years of age. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-12 years must be increased. Universal vaccination against varicella in the second year of life is an effective strategy, and the immediate public availability of the vaccine is requested in order to guarantee the right of healthy children to be vaccinated. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. The recently authorised meningococcal B vaccine has opened a chapter of hope in the

  11. Effect of oral cephalexin in the treatment of BCG lymphadenitis.

    Science.gov (United States)

    Ayazi, Parviz; Mahyar, Abolfazl; Taremiha, Alireza; Ghorani, Najmeh; Esmailzadehha, Neda

    2014-06-01

    Lymphadenitis and abscess formation are the most common side effects of vaccination with Bacille Calmette Guerin (BCG). The lower the child's age at the time of vaccination, the higher the incidence of BCG lymphadenitis tends to be. Although various therapeutic approaches are in use for the treatment of BCG lymphadenitis, there is no consensus on which of them is optimal. This study aimed to determine whether oral cephalexin treatment hastens recovery from BCG lymphadenitis. The study involved 40 children (24 boys and 16 girls) with BCG lymphadenitis who were referred to Qazvin Children's Hospital, Qazvin University of Medical Sciences between December 2008 and the end of September 2009. The patients were randomly assigned to two groups of 20 patients each (12 boys and 8 girls in each group): group A patients did not receive any treatment and served as controls, and group B patients were treated with 50 mg/kg/day cephalexin syrup, administered in four doses, for 10 days. In all patients, clinical examination was normal, except for lymphadenitis. In all patients, BCG vaccination had been performed at birth, and polymerase chain reaction tests were positive for tuberculous bacilli. The recovery period and requirement of fine needle aspiration did not significantly differ between the two groups (P 0.05). This study showed that treatment with cephalexin does not hasten recovery from BCG lymphadenitis.

  12. BCG Induced Necrosis of the Entire Bladder Urothelium

    Directory of Open Access Journals (Sweden)

    Malte Krönig

    2015-09-01

    Full Text Available Instillation therapy with attenuated tuberculosis bacteria (BCG can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence.

  13. Hubungan antara Pembentukan Scar Vaksin BCG dan Kejadian Infeksi Tuberkulosis

    Directory of Open Access Journals (Sweden)

    Fajriah Rosandali

    2016-08-01

    Full Text Available AbstrakTuberkulosis adalah penyakit menular yang disebabkan oleh kuman Mycobacterium tuberculosis. Orang dewasa yang menderita tuberkulosis sangat mudah menularkan kuman TB kepada orang disekitarnya terutama pada anak-anak. Salah satu cara pencegahan penyakit tuberkulosis adalah pemberian imunisasi BCG pada saat bayi baru lahir. Scar vaksin BCG dapat terbentuk setelah penyuntikan, kadang Scar tidak terbentuk setelah penyuntikan. Tujuan penelitian ini adalah menentukan hubungan antara pembentukan Scar vaksin BCG dan kejadian infeksi tuberkulosis. Penelitian ini menggunakan desain cross sectional dengan jumlah subjek sebanyak 80 orang. Pengambilan data berupa melakukan pengamatan terhadap Scar pada lengan atas serta wawancara kepada responden dengan menggunakan pedoman wawancara. Kemudian data ditabulasi dalam bentuk persentase dan dianalisis dengan uji chi-square . Hasil penelitian menunjukan bahwa responden yang terbanyak adalah perempuan dan usia yang terbanyak 35-44 tahun. Terdapat hubungan yang bermakna antara pembentukan Scar  vaksin BCG dengan kejadian infeksi tuberkulosis (p < 0,05. Disimpulkan bahwa terdapat pengaruh antara pembentukan Scar vaksin BCG terhadap kejadian infeksi tuberkulosis.Kata kunci: tuberkulosis, vaksin BCG, Scar. AbstractTuberculosis is an infectious disease caused by Mycobacterium tuberculosis with the number of sufferers tend to increase every years. Adults who suffer  tuberculosis is very easy to spread it to around, especially to children. One of the way to prevent tuberculosis is immunization of BCG vaccine which given since infant. The Scar of BCG vaccine can formed after injection or not. The objective of this study was to determine the relation of BCG vaccine Scar formation on  the incidence of tuberculosis infection.This research used a cross sectional design with 80 total subjects. The data was collected by observations of the scar on the upper arm while interviewed  respondents using interview guide

  14. [Modifications by BCG of the mortality of the irradiated mouse].

    Science.gov (United States)

    Allain, P; Chaleil, D; Maingot, D; Larra, F

    1976-01-01

    Freeze-dried Bacillus Calmette Guerin (B.C.G.) of Institut Pasteur was given by intravenous route to mice at 1,2 and 4 mg/kg before and after gamma irradiation of animals by 1 000 rad. B.C.G. 1 mg/kg injected the day or the day after irradiation has a protective effect (mortality reduced from 77% for controls to 58% and 50% for treated mice). B.C.G. given before irradiation in single or double doses increased mortality.

  15. Infant Feeding among Women Attending an Immunisation Clinic at a Tertiary Health Institution in Ibadan, Nigeria

    Science.gov (United States)

    Fatiregun, A. A.; Abegunde, V. O.

    2009-01-01

    Maternal characteristics can affect a mother's decision to breastfeed. This study used a cross-sectional design to assess maternal variables and infant feeding patterns among nursing mothers attending an immunisation clinic in Ibadan, Nigeria. A total of 264 mothers who consecutively attended the immunisation clinic and met certain inclusion…

  16. Growth enhancement of rainbow trout (Oncorhynchus mykiss) by passive immunisation against somatostatin-14

    Science.gov (United States)

    Juvenile rainbow trout (Oncorhynchus mykiss) were passively immunised against somatostatin-14 (SS-14) using an antibody originating from egg laying chicken (Gallus domesticus). Fish were immunised weekly (0, 7, 14, 21, 28, 35 d) with chicken egg yolk derived immunoglobulin (IgY) against SS-14 (1:25 ...

  17. More support for mothers: a qualitative study on factors affecting immunisation behaviour in Kampala, Uganda

    Directory of Open Access Journals (Sweden)

    Wamani Henry

    2011-09-01

    Full Text Available Abstract Background The proportion of Ugandan children who are fully vaccinated has varied over the years. Understanding vaccination behaviour is important for the success of the immunisation programme. This study examined influences on immunisation behaviour using the attitude-social influence-self efficacy model. Methods We conducted nine focus group discussions (FGDs with mothers and fathers. Eight key informant interviews (KIIs were held with those in charge of community mobilisation for immunisation, fathers and mothers. Data was analysed using content analysis. Results Influences on the mother's immunisation behaviour ranged from the non-supportive role of male partners sometimes resulting into intimate partner violence, lack of presentable clothing which made mothers vulnerable to bullying, inconvenient schedules and time constraints, to suspicion against immunisation such as vaccines cause physical disability and/or death. Conclusions Immunisation programmes should position themselves to address social contexts. A community programme that empowers women economically and helps men recognise the role of women in decision making for child health is needed. Increasing male involvement and knowledge of immunisation concepts among caretakers could improve immunisation.

  18. Relationship between parent held child records for immunisations, parental recall and health service.

    LENUS (Irish Health Repository)

    Jessop, L

    2011-03-01

    Parent held child records (PHCR) were introduced in Ireland in 2008. This study investigated the relationship between the PHCR, parental recall and regional Health Service Executive (HSE) records for immunisation uptake. It used the Lifeways cohort study of 1070 singleton children to compare immunisation data from PHCR at one year, parental recall at five years and information from the HSE. When compared to HSE records, full recording of primary immunisations in the PHCR was reported for 695 of 749 (92.8%) children. Parental recall was correct for 520 of 538 (96.7%) children. Of the 307 completed PHCRs, 207 (75.9%) agreed with the HSE records. Agreement between the three sources for primary immunisations was 74-93% but was not statistically significant. Agreement was 91% (p < 0.001) for measles, mumps and rubella (MMR) vaccines between parental recall and HSE records. PHCRs underestimated and parental recall overestimated immunisation status when compared with HSE records.

  19. The Abell 85 BCG: a nucleated, core-less galaxy

    CERN Document Server

    Madrid, Juan P

    2016-01-01

    New high-resolution r band imaging of the brightest cluster galaxy (BCG) in Abell 85 (Holm 15A) was obtained using the Gemini Multi Object Spectrograph. These data were taken with the aim of deriving an accurate surface brightness profile of the BCG of Abell 85, in particular its central region. The new Gemini data show clear evidence of a previously unreported nuclear emission that is evident as a distinct light excess in the central kiloparsec of the surface brightness profile. We find that the light profile is never flat nor does it present a downward trend towards the center of the galaxy. That is, the new Gemini data show a different physical reality from the featureless, "evacuated core" recently claimed for the Abell 85 BCG. After trying different models, we find that the surface brightness profile of the BCG of Abell 85 is best fit by a double Sersic model.

  20. SIMULTANEOUS SMALLPOX AND B.C.G. VACCINATION IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Nyoman Kumara Rai

    2012-09-01

    Full Text Available Vaksinasi cacar dan BCG mulai diberikan secara simultan di Jawa dan Bali pada bulan April 1972 vaksinasi cacar diberikan pada lengan kiri dan BCG pada lengan kanan. Secara berangsur-angsur prograi ini kemudian diperluas kedaerah luar Jawa-Bali, sehingga pada akhir tahun 1973 sudah mencakup seluruh Indonesia. Tenaga yang digunakan adalah para juru cacar yang sudah ada dalam rangka proyek pembasmian penyakit cacar yang dimulai tahun 1968, dan terdapat hampir disemua kecamatan diseluru Indonesia. Ide untuk menggabungkan kedua jenis vaksinasi ini yang kebetulan mempunyai target sam (anak2 0 - 14 thn  timbul setelah penderita cacar tidak dilaporkan lagi dibulan September 1971 (ternyata kemudian letusan cacar terakhir adalah dibulan Desember 1971. Sampai saat itu vaksina BCG dilakukan oleh petugas Puskesmas dan tenaga part timer. Ternyata target tidak pernah tercapa hal ini mungkin disebabkan oleh terbatasnya waktu yang tersedia untuk melakukan vaksinasi BCC sehingga para tenaga part timer tsb. hanya mampu mencakup daerah disekitar Puskesmas dan sekolah dasar. Sebelumnya telah diadakan dua trial; yang pertama diadakan di Bandung untuk melihat at tidaknya saling pengaruh mempengaruhi antara kedua jenis vaksin cacar dan BCG bila diberikan pat saat yang bersamaan, sedangkain trial kedua dilakukan untuk menilai kemampuan juru cacar dala melaksanakan vaksinasi BCG serta kesukaran! yang dijumpai dilapangan (masing2 didua kabupaten (Jawa Tengah, Timur dan Yogyakarta. Disamping keuntungan yang diperoleh dari penggabungan kedua jenis vaksinasi ini yakni penghematan tenaga, biaya dan waktu, dijumpai juga beberapa kesukaran antara lain pengumpulan anak2, supply vaksin BCG yang tidak teratur dll. Walaupun demikian, di Jawa dan Bali hasil vaksinasi BCG antara April 1972 sampai dengan April 1973 menunjukkan kenaikan out-put leb dari 4 kali lipat bila dibandingkan dengan out-put sebelum penggabungan, meskipun out-put prin vaksinasi cacar mempunyai tendensi menurun

  1. Disseminated BCG infection in a patient with severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Han, Tae Il [Eulji University School of Medicine, Taejon (Korea, Republic of); Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2000-06-01

    Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy.

  2. Disseminated BCG Infection in a patient with Severe Combined Immunodeficiency

    OpenAIRE

    Han, Tae Il; Kim, In-One; Kim, Woo Sun; Yeon, Kyung Mo

    2000-01-01

    Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) vaccination is a very rare disorder, occurring mostly in patients with immunologic deficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy.

  3. Rotavirus vaccination within the South African Expanded Programme on Immunisation.

    Science.gov (United States)

    Seheri, L Mapaseka; Page, Nicola A; Mawela, Mothahadini P B; Mphahlele, M Jeffrey; Steele, A Duncan

    2012-09-07

    Diarrhoeal diseases are ranked the third major cause of childhood mortality in South African children less than 5 years, where the majority of deaths are among black children. Acute severe dehydrating rotavirus diarrhoea remains an important contributor towards childhood mortality and morbidity and has been well documented in South Africa. As the preventive strategy to control rotavirus diarrhoea, South Africa became the first country in the WHO African Region to adopt the rotavirus vaccine in the national childhood immunisation programme in August 2009. The rotavirus vaccine in use, Rotarix, GSK Biologicals, is given at 6 and 14 weeks of age, along with other vaccines as part of Expanded Programme on Immunisation (EPI). Studies which facilitated the introduction of rotavirus vaccine in South Africa included the burden of rotavirus disease and strain surveillance, economic burden of rotavirus infection and clinical trials to assess the safety and efficacy of vaccine candidates. This paper reviews the epidemiology of rotavirus in South Africa, outlines some of the steps followed to introduce rotavirus vaccine in the EPI, and highlights the early positive impact of vaccination in reducing the rotavirus burden of disease based on the post-marketing surveillance studies at Dr George Mukhari hospital, a sentinel site at University of Limpopo teaching hospital in Pretoria, South Africa, which has conducted rotavirus surveillance for >20 years.

  4. SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

    Directory of Open Access Journals (Sweden)

    Abdul Rivai

    2012-09-01

    Full Text Available Telah dikemukakan anggapan-anggapan yang terdapat dewasa ini tentang vaksinasi BCG dan cacar secara simultan. Telah dilakukan vaksinasi BCG dan cacar secara simultan pada 729 neonati dengan freeze dried Smallpox vaccine buatan dari Bio Farma dan freeze dried BCG vaccine Tokyo. Pencacaran dilakukan secara multiple puncture dan bifurcated needle dengan suntikan BCG dengan jarum dan spuit khusus intracutan dengan dosis 0,1 ml. Tuberkulin test dilakukan dengan PPD dari Kopenhagen dengan kekuatan 2 TU 9 minggu setelah vaksinasi. Dari 741 bayi yang diikut sertakan dalam survey, 12 menolak, 3 bayi tidak dapat dilakukan pemeriksaan pertama, 35 bayi belum diperiksa, pemeriksaan pertama telah dilakukan pada 691 bayi. Dari 406 bayi yang seharusnya sudah diperiksa untuk pemeriksaan kedua, 23 dapat dilakukan karena tidak dapat dijumpai atau meninggal. Telah dikemukakan bahwa pencatatan alamat yang jelas dan lengkap serta kesungguhan dalam melakukan home visits sangat penting untuk berhasilnya penyelidikan semacam ini. Dari hasil-hasil yang didapatkan sampai sekarang telah dapat diambil kesimpulan sementara, bahwa vaksinasi BCG dan cacar secara simultan memberikan hasil yang memuaskan, juga bila dibandingkan dengan hasil-hasil penyelidikan diluar negeri take pada pencacaran 99.4 percent, test tuberkulin dengan PPD 2 TU 9 minggu setelah vaksinasi memberikan indurasi lebih dari 5 mm pada 99.75 percent dan tidak menimbulkan komplikasi-komplikasi. Pelaksanaan vaksinasi BCG dan cacar dapat dilakukan oleh tenaga paramedis yang telah mendapat latihan khusus dan diawasi oleh dokter yang kompeten. Dianjurkan untuk melakukan follow up pada bayi-bayi yang diikut sertakan dalam survey ini.

  5. Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    S. Lukacs

    2013-01-01

    Full Text Available Intravesical Bacilli Calmette-Guérin (BCG immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin, he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

  6. Fiscal consequences of changes in morbidity and mortality attributed to rotavirus immunisation.

    Science.gov (United States)

    Kotsopoulos, Nikolaos; Connolly, Mark P; Postma, Maarten J; Hutubessy, Raymond C W

    2013-11-04

    Changes in population health status are known to influence government fiscal transfers both in terms of lost tax revenue and increased expenditure for health and social services. To estimate the fiscal impact of changes in morbidity and mortality attributed to rotavirus immunisation, we developed a government perspective model to estimate discounted net tax revenue for Ghana and Vietnam. The model derived the impact of rotavirus morbidity and mortality on lifetime productive capacity and related tax transfers, and demand for government transfers in relation to education and healthcare in immunised and non-immunised cohorts. The discounted age-specific net tax revenue was derived by deducting transfers from gross taxes and discounting for time preference. In Ghana, taking into account immunisation costs, tax and transfers, the estimated net discounted tax for the immunised cohort was estimated to generate $2.6 billion in net taxes up to age 65. In Vietnam, the net revenue attributed to the immunised cohort reached $55.17 billion suggesting an incremental benefit of approximately $29 million. We posit that the government perspective fiscal framework described here is a valid approach for estimating how governments benefit from investments in immunisation that can be considered supplementary to conventional cost-effectiveness approaches for defining value.

  7. BCG pneumonitis with a miliary radiological pattern complicating intravesical BCG immunotherapy

    Directory of Open Access Journals (Sweden)

    Evangelia Fouka

    2010-01-01

    Full Text Available SUMMARY. The case is described of a 42 year-old male who presented with fever, haematuria, hypoxaemia, impaired liver function and a miliary pattern on chest X-ray while receiving intravesical BCG treatment for superficial bladder cancer. Initiation of antituberculous therapy resulted in rapid amelioration of the symptoms and the X-ray findings, and the patient left hospital in a good general state of health. Although M. bovis was not isolated from samples of sputum, bronchioalveolar lavage fluid (BALF or bronchial biopsy tissue, the prompt response to antituberculous therapy suggests an infectious aetiology due to microbial dissemination. Pneumon 2010, 23(4:388-391.

  8. BCG and the treatment of superficial bladder cancer.

    Science.gov (United States)

    Moss, J T; Kadmon, D

    1991-12-01

    In this report, we review the evolution of bacillus Calmette-Guérin (BCG) immunotherapy as a legitimate form of treatment in superficial, nonmuscle-invasive bladder cancer. In the US, an estimated 45,000 new cases of bladder cancer are diagnosed each year and the annual death rate approaches 11,000. Approximately 70 percent of these cancers are superficial at the time of initial presentation. The treatment of superficial bladder cancer has three objectives: (1) eradication of existing disease, (2) prophylaxis against tumor recurrence, and (3) prevention of tumor progression (either muscular invasion, metastatic spread, or both). Cystectomy generally is reserved for muscle-invasive disease. Transurethral resection of the bladder tumor is the preferred initial therapy. Intravesical instillations of various chemotherapeutic agents following transurethral resection have been extensively investigated. Some of the common agents used include thiotepa, mitomycin, and doxorubicin. Despite such treatment efforts, however, over 40 percent of patients with superficial bladder cancer experience a recurrence of their tumor within three years. Approximately half of these recurrences either present as less-well-differentiated tumors or have already penetrated into the bladder musculature, metastasized, or both. Since Morales et al. first introduced intravesical BCG vaccine for prophylaxis as well as for treatment of superficial bladder tumors in 1976, support has grown rapidly for its use as an alternative to chemotherapy. When used with prophylactic intent following transurethral resection, recurrence rates are lower than those achieved with other agents. In addition, BCG is emerging as the consensus drug of choice for treating carcinoma in situ of the bladder. The mechanisms by which BCG exerts its antitumor activity remain largely unknown. BCG is thought to stimulate a localized, nonspecific inflammatory response that leads to subsequent shedding of tumor cells. A large body

  9. Investigation of granulomatous prostatitis incidence following intravesical BCG therapy

    Science.gov (United States)

    Balasar, Mehmet; Doğan, Metin; Kandemir, Abdulkadir; Taskapu, Hakan Hakki; Cicekci, Faruk; Toy, Hatice; Gurbuz, Recai

    2014-01-01

    In the present manuscript, we studied the incidence of granulomatous prostatitis in the prostatectomy specimen of the patients who underwent transurethral resection of the prostate (TURP) after superficial bladder cancer treatment with intravesical Bacillus Calmette-Guerin (BCG) and were diagnosed with benign prostate hyperplasia (BPH). The clinical data and histopathological specimen records of 472 patients who underwent TUR-P due to BPH diagnosis, obtained over a period of 6 years in the urology department of Private Konya Hospital, Konya, Turkey, were studied retrospectively. The cases were divided into two groups as (Group I) who did not undergo any treatment and as (Group II) who underwent BCG treatment. The frequency and the clinical course of the cases with granulomatous prostatitis were studied histopathologically. There were in total 472 patients who underwent TUR-P. Out of the 459 patients who did not undergo BCG treatment (Group I), the histopathological specimen records of 262 (57%) was BPH, of 197 (43%) BPH + chronic prostatitis. Of the second group, 13 cases underwent intravesical BCG treatment before surgical intervention due to superficial bladder CA diagnosis. In this group 4 of the cases were diagnosed as (30%) BPH, 9 as (70%) chronic prostatitis + BPH. 6 out of the 9 chronic prostatitis cases were chronic prostatitis, 2 caseous granulomatous prostatitis, 1 non-caseous granulomatous prostatitis. Granulomatous prostatitis cases should require no specific therapy. Conclusion: In patients with obstruction complaints following intravesical BCG treatment, granulomatous prostatitis should also be considered and treatment plans should be made accordingly. PMID:25035779

  10. Comparative Proteomic Profiling of Mycobacterium bovis and BCG Vaccine Strains

    KAUST Repository

    Gao, Ge

    2013-09-01

    BCG is the only licensed human vaccine currently available against TB. Derived from a virulent strain of M. bovis, the vaccine was thought to have struck a balance between reduced virulence and preserved immunogenicity. Nowadays, BCG vaccine strains used in different countries and vaccination programs show clear variations in their genomes and immune protective properties. The aim of this study was to characterize the proteomic profile on Mycobacterium bovis and five BCG strains Pasteur, Tokyo, Danish, Phipps and Birkhaug by Tandem Mass Tag® (TMT®)-labeling quantitative proteomic approach. In total, 420 proteins were identified and 377 of them were quantitated for their relative abundance. We reported the number and relationship of differential expressed proteins in BCG strains compared to M. bovis and investigated their functions by bioinformatics analysis. Several interesting up-regulated and down-regulated protein targets were found. The identified proteins and their quantitative expression profiles provide a basis for further understanding of the cellular biology of M. bovis and BCG vaccine strains, and hopefully would assist in the design of better anti-TB vaccine and drugs.

  11. The long-term efficacy of hepatitis B immunisation in aneasthetists in Bloemfontein

    Directory of Open Access Journals (Sweden)

    J. H. S. van der Merwe

    1988-03-01

    Full Text Available Thirty three months after vaccination, protective immunity was present in only 47 of anaesthetists immunised with plasma-derived vaccine. It appears that the age of the vaccinee is a major adverse factor.

  12. Fifty years of immunisation in Australia (1964-2014): the increasing opportunity to prevent diseases.

    Science.gov (United States)

    Royle, Jenny; Lambert, Stephen B

    2015-01-01

    Medicine has seen dramatic changes in the last 50 years, and vaccinology is no different. Australia has made a significant contribution to world knowledge on vaccine-preventable diseases. Certain deadly diseases have disappeared or become rare in Australia following successful introduction of vaccines. As diseases become rarer, public knowledge about the diseases and their serious consequences has decreased, and concerns about potential vaccine side effects have increased. To maintain confidence in immunisations, sharing of detailed information about the vaccines and the diseases we are trying to prevent is integral to the continued success of our public health programme. Modern quality immunisation programmes need to communicate complex information to immunisation providers and also to the general community. Improving immunisation coverage rates and eliminating the gap in coverage and timeliness between Aboriginal and Torres Strait Islander peoples and non-Indigenous people has become a high priority.

  13. Disseminated Bacille Calmette-Guerin (BCG) disease in an infant with severe combined immunodeficiency.

    Science.gov (United States)

    Sohail, Shagufta; Afzal, Muhammad; Anwar, Vaqas; Shama, Quratulain

    2014-11-01

    Bacille Calmette-Guerin (BCG) vaccine is administered to all newborns in countries where tuberculosis is still endemic. It is a live attenuated vaccine and considered quite safe in immunocompetent children. Disseminated BCG disease is the most serious complication seen only in individuals with underlying primary or secondary immunodeficiencies. We report a case of disseminated BCG disease in an infant with Severe Combined Immunodeficiency (SCID) who received BCG administration prior to diagnosis of SCID.

  14. Interventions for improving coverage of childhood immunisation in low- and middle-income countries

    OpenAIRE

    Oyo-ita, Angela; Wiysonge, Charles S; Oringanje, Chioma; Nwachukwu, Chukwuemeka E; Oduwole, Olabisi; Meremikwu, Martin M

    2016-01-01

    Background Immunisation is a powerful public health strategy for improving child survival, not only by directly combating key diseases that kill children but also by providing a platform for other health services. However, each year millions of children worldwide, mostly from low- and middle-income countries (LMICs), do not receive the full series of vaccines on their national routine immunisation schedule. This is an update of the Cochrane review published in 2011 and focuses on intervention...

  15. Parental perceptions of school-based influenza immunisation in Ontario, Canada: a qualitative study

    OpenAIRE

    MacDougall, Donna; Crowe, Lois; Jennifer A Pereira; Kwong, Jeffrey C.; Quach, Susan; Wormsbecker, Anne E; Ramsay, Hilary; Salvadori, Marina I; Russell, Margaret L; ,

    2014-01-01

    Objective To understand the perspectives of Ontario parents regarding the advantages and disadvantages of adding influenza immunisation to the currently existing Ontario school-based immunisation programmes. Design Descriptive qualitative study. Participants Parents of school-age children in Ontario, Canada, who were recruited using a variety of electronic strategies (social media, emails and media releases), and identified as eligible (Ontario resident, parent of one or more school-age child...

  16. Enhancement of Leishmania amazonensis infection in BCG non-responder mice by BCG-antigen specific vaccine

    Directory of Open Access Journals (Sweden)

    Kátia da Silva Calabrese

    1992-01-01

    Full Text Available Different patterns of cutaneous leishmaniasis can be induced when a challenge of alike dose of Leishmania amazonensis amastigotes in various inbred strains was applied. Two strains of mice, the Balb/c and C57 BL/10J, showed exceptional suscepbility, and 10(elevado a sexta potência amastigotes infective dose lead, to ulcerative progressive lesions with cutaneous metastasis and loss by necrosis of leg on wich the footpad primary lesion occured. Lesions were also progressive but in a lower degree when C3H/HeN and C57BL/6 were infected. Lesions progress slowly in DBA/2 mice presenting lesions wich reach a discreet peack after 12 weeks, do not heal but do not uncerate. DBA/2 mice is, therefore, a good model for immunomodualtion. In attempt to determine the influence of BCG in vaccination schedule using microsomal fraction, DBA/2 became an excellent model, since it is also a non-responder to BCG. Vaccination of DBA/2 mice, receiving the same 10(elevado a sexta potência BCG viable dose and 10 *g or 50 *g of protein content of microsomal fraction, lead to a progressive disease with time course similar to those observed in susceptible non-vaccinated C57BL/10J mice after 6 months of observation. An enhancement of infection in BCG non-responder mice suggests that use of BCG as immunostimulant in humans could be critical for both vaccination and immunoprophylactic strategies.

  17. Different effects of BCG strains - A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau

    DEFF Research Database (Denmark)

    Frankel, H; Byberg, S; Andersen, Morten Bjerregaard;

    2016-01-01

    models. Scar prevalence and size were compared using binomial regression and ranksum tests. RESULTS: Among 1206 children, 18% received Danish BCG (n=215) and 82% Russian BCG (n=991). The adjusted hazard ratio (aHR) for consultations was 0.94 (95% CI 0.60-1.46) for Danish BCG compared with Russian BCG......BACKGROUND: Different Bacillus Calmette-Guerin (BCG) vaccine strains may have different non-specific effects. We assessed the effect of two BCG strains (Danish and Russian) on childhood morbidity and BCG scarification in Guinea-Bissau. METHODS: During 2011-2013, infants in the Bandim Health Project....... Girls vaccinated with Danish BCG tended to have lower consultation rates compared with girls vaccinated with Russian BCG (aHR 0.56 (0.25-1.24)), whereas the effect was opposite for boys (aHR 1.24 (0.74-2.11)), p=0.09. Children vaccinated with Danish BCG were more likely to develop a scar (97%) than...

  18. BCG vaccination scar associated with better childhood survival in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Gustafson, Per; Nhaga, Alexandro

    2005-01-01

    Recent studies have suggested that Bacille Calmette-Guerin (BCG) vaccination may have a non-specific beneficial effect on infant survival and that a BCG scar may be associated with lower child mortality. No study has previously examined the influence of BCG vaccination on cause of death....

  19. Nanoparticulation of BCG-CWS for application to bladder cancer therapy

    OpenAIRE

    Nakamura, Takashi; Fukiage, Masafumi; Higuchi, Megumi; NAKAYA, Akihiro; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Ito, Toshihiro; Hosokawa, Hiroyuki; Nakayama, Toshinori; Harashima, Hideyoshi

    2014-01-01

    The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of mu m, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166 nm-sized lipid particles. The BCG-CWS encapsulated nano parti...

  20. Role of fibronectin in intravesical BCG therapy for superficial bladder cancer.

    Science.gov (United States)

    Ratliff, T L; Kavoussi, L R; Catalona, W J

    1988-02-01

    Intravesical bacillus Calmette-Guerin (BCG) has been demonstrated to be effective both for prophylaxis and treatment of superficial bladder cancer. In order to identify the progression of events that result in BCG-mediated antitumor activity, studies were performed to evaluate the mechanism of binding of BCG within the bladder. Histological and quantitative studies in a mouse model revealed that BCG attached to the bladder wall only in areas of urothelial damage. Preliminary in vitro data showed that BCG attached to surfaces coated with extracellular matrix proteins. Further studies were then performed using purified extracellular matrix proteins to identify the proteins responsible for attachment. BCG were observed to attach to surfaces coated only with purified fibronectin (FN) but not to other purified proteins including laminin, collagen or fibrinogen. The attachment of BCG to purified FN in vitro was dose dependent and was inhibited by anti-FN antibodies. Moreover, BCG attachment in vivo to bladders with damaged urothelial surfaces was inhibited more than 95% by anti-FN antibodies, but binding was not affected by anti-laminin antibodies or preimmune serum. A survey of commercially available BCG vaccines (Pasteur, Tice, Glaxo, Connaught) showed that only Glaxo BCG did not attach to FN-coated surfaces. Glaxo BCG also was shown to express inferior antitumor activity suggesting that the absence of FN binding by Glaxo may have been associated with the absence of antitumor activity of the vaccine.

  1. Passive immunisation, an old idea revisited: Basic principles and application to modern animal production systems.

    Science.gov (United States)

    Hedegaard, Chris J; Heegaard, Peter M H

    2016-06-01

    Immunisation by administration of antibodies (immunoglobulins) has been known for more than one hundred years as a very efficient means of obtaining immediate, short-lived protection against infection and/or against the disease-causing effects of toxins from microbial pathogens and from other sources. Thus, due to its rapid action, passive immunisation is often used to treat disease caused by infection and/or toxin exposure. However immunoglobulins may also be administered prior to exposure to infection and/or toxin, although they will not provide long-lasting protection as is seen with active immunisation (vaccination) in which an immunological memory is established by controlled exposure of the host to the pathogen in question. With multi-factorial infectious diseases in production animals, especially those that have proven hard to control by vaccination, the potential of passive immunisation remains big. This review highlights a number of examples on the use of passive immunisation for the control of infectious disease in the modern production of a range of animals, including pigs, cattle, sheep, goat, poultry and fish. Special emphasis is given on the enablement of passive immunisation strategies in these production systems through low cost and ease of use as well as on the sources, composition and purity of immunoglobulin preparations used and their benefits as compared to current measures, including vaccination (also comprising maternal vaccination), antibiotics and feed additives such as spray-dried plasma. It is concluded that provided highly efficient, relatively low-price immunoglobulin products are available, passive immunisation has a clear role in the modern animal production sector as a means of controlling infectious diseases, importantly with a very low risk of causing development of bacterial resistance, thus constituting a real and widely applicable alternative to antibiotics.

  2. Estimating vaccination coverage in the absence of immunisation registers--the German experience.

    Science.gov (United States)

    Siedler, A; Rieck, T; Reuss, A; Walter, D; Poggensee, G; Poethko-Muller, C; Reiter, S

    2012-04-26

    Immunisation registers are regarded as an appropriate solution to measure vaccination coverage on a population level. In Germany, a decentralised healthcare system and data protection regulations constrain such an approach. Moreover, shared responsibilities in the process of immunisation and multiple providers form the framework for public health interventions on vaccination issues. On the national level, those interventions consist mainly of conceptualising immunisation strategies, establishing vaccination programmes, and issuing recommendations. This paper provides an overview on sources and methods for collecting appropriate coverage data at national level and their public health relevance in Germany. Methods of data collection and available information on immunisations are described for three approaches: school entrance health examination, population surveys and insurance refund claim data. School entrance health examinations allow regional comparisons and estimation of trends for a specific cohort of children and for all recommended childhood vaccinations. Surveys deliver population based data on completeness and timeliness of selected vaccinations in populations defined by age or socio-demographic parameters and on knowledge and attitudes towards vaccination. Insurance refund claim data inform continuously on immunisation status (e.g. of children aged two years) or on vaccination incidence promptly after new or modified recommendations. In a complex healthcare system, the German National Public Health Institute (Robert Koch Institute, RKI) successfully compiles coverage data from different sources, which complement and validate one another. With the German approach of combining different data sources in the absence of immunisation registers, it is possible to gain solid and reliable data on the acceptance of vaccination programmes and target groups for immunisation. This approach might be of value for other countries with decentralised healthcare systems.

  3. The past, current and future trends in DNA vaccine immunisations

    Directory of Open Access Journals (Sweden)

    Sidgi Syed Anwer Abdo Hasson

    2015-05-01

    Full Text Available This review focuses on DNA vaccines, denoting the last two decades since the early substantiation of preclinical protection was published in Science in 1993 by Ulmer et al. In spite of being safely administered and easily engineered and manufactured DNA vaccine, it holds the future prospects of immunization by inducing potent cellular immune responses against infectious and non-infectious diseases. It is well documented that injection of DNA plasmid encoding a desired gene of interest can result in the subsequent expression of its products and lead to the induction of an immune response within a host. This is pertinent to prophylactic and therapeutic vaccination approach when the peculiar gene produces a protective epitope from a pathogen. The recent studies demonstrated by a number of research centers showed that these immune responses evoke protective immunity against several infectious diseases and cancers, which provides adequate support for the use of this approach. We attempt in this review to provide an informative and unbiased overview of the general principles and concept of DNA vaccines technology with a summary of a novel approach to the DNA vaccine, present investigations that describe the mechanism(s of protective immunity provoked by DNA immunization and to highlight the advantages and disadvantages of DNA immunisation.

  4. The past, current and future trends in DNA vaccine immunisations

    Institute of Scientific and Technical Information of China (English)

    Sidgi; Syed; Anwer; Abdo; Hasson; Juma; Khalifa; Zayid; Al-Busaidi; Talal; Abdulmalek; Sallam

    2015-01-01

    This review focuses on DNA vaccines, denoting the last two decades since the early substantiation of preclinical protection was published in Science in 1993 by Ulmer et al. In spite of being safely administered and easily engineered and manufactured DNA vaccine, it holds the future prospects of immunization by inducing potent cellular immune responses against infectious and non-infectious diseases. It is well documented that injection of DNA plasmid encoding a desired gene of interest can result in the subsequent expression of its products and lead to the induction of an immune response within a host. This is pertinent to prophylactic and therapeutic vaccination approach when the peculiar gene produces a protective epitope from a pathogen. The recent studies demonstrated by a number of research centers showed that these immune responses evoke protective immunity against several infectious diseases and cancers, which provides adequate support for the use of this approach. We attempt in this review to provide an informative and unbiased overview of the general principles and concept of DNA vaccines technology with a summary of a novel approach to the DNA vaccine, present investigations that describe the mechanism(s) of protective immunity provoked by DNA immunization and to highlight the advantages and disadvantages of DNA immunisation.

  5. Socio cultural and geographical determinants of child immunisation in Borno State, Nigeria

    Directory of Open Access Journals (Sweden)

    Abubakar Kawu Monguno

    2013-09-01

    Full Text Available Immunisation has been an important strategy for disease prevention globally. Despite proven successes in other settings, child immunisation has continued to be problematic in developing countries including Nigeria. In addressing the problems, policy in Nigeria is largely directed at overcoming socio cultural issues surrounding parents’ rejection of vaccines. However, determinants of immunisation have geographical implications as well. A cross sectional survey was used to select 484 mothers/ caregivers through a multi stage cluster sampling technique from the three senatorial districts of Borno State, Nigeria. Mothers or caregivers of children 12–23 months were interviewed using a structured questionnaire adapted from the Nigeria Demographic and Health Survey (2008. Socio cultural factors measured include mother’s education, religion, husband’s permission and sex of child while spatial variables include location i.e. whether rural or urban, and distance measured in terms of physical distance, cost and perception of physical distance. Descriptive statistics, univariate and multivariate logistic regressions were used to analyse the results. Data indicate that only 10.5% of children were fully immunised. Though immunisation uptake differed between the senatorial districts, this was not significant (P=0.1. In the bivariate analysis, mothers living in urban areas, <1 km to immunisation centre, their perception of travel distance and travel cost were the spatial predictors of immunisation while literacy and husband’s permission were the socio-cultural factors of significance. However, in the multivariate regression only two geographical factors i.e. living in an urban area [odds ratio (OR 3.42, confidence interval (CI 1.40–8.33] and mothers’ perception of distance (OR 4.52, CI 2.14–9.55 were protective against under immunisation while mother’s education was the only socio cultural variable of significance (OR 0.10, CI 0.03–0.41. It

  6. Inhibitory effect of BCG cell-wall skeletons (BCG-CWS) emulsified in squalane on tumor growth and metastasis in mice.

    Science.gov (United States)

    Yoo, Yung Choon; Hata, Katsusuke; Lee, Kyung Bok; Azuma, Ichiro

    2002-08-01

    The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis showed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the antimetastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

  7. Inform or Not? An Exploratory Study of Motivations in Mothers for the Information Given to Their Toddlers before Immunisation

    Science.gov (United States)

    Favez, Nicolas; Newman, Claire

    2014-01-01

    Toddlers experience stress and express distress during routine paediatric examinations with immunisation. Adjustment to this situation is important, as distress and pain are interrelated. A negative experience of immunisation of their child, moreover, is often mentioned by parents as a reason for refusing routine vaccinations. This paper focuses…

  8. Effectiveness of BCG Vaccination in Prevention of Childhood Tuberculosis: A Prospective Study from Kishanganj, Bihar

    Directory of Open Access Journals (Sweden)

    Kashif Shahnawaz, Goutam Sarkar, Palash Das, Mausumi Basu, Biman Roy

    2013-01-01

    Full Text Available Introduction: BCG vaccine has shown consistently high efficacy against childhood tubercular meningitis and miliary tuberculosis and other mycobacterial diseases. It is considered to be a safe vaccine with a low incidence of adverse effects. Efficacy of BCG vaccine found in different clinical trials is variable in different geography. Objectives: Study was done to assess the efficacy of BCG vac-cine. Materials and Methods: All the children who were less than three years of age and were previously BCG vaccinated and not-vaccinated, were included in this study. A total of sixty (60 vaccinated children and sixty non-vaccinated children were selected. These children were followed up prospectively for 24 months, at the end of which, it was seen whether they developed tuberculosis or not. Results: Out of these 60 children in both the cases and control groups, total number of BCG vaccinated children who developed TB were 4 (i.e. 6.6% and total number of Non-BCG vaccinated children who developed TB were 12 (i.e. 20%. Thus, the efficacy of BCG vaccine calculated in our study was 67%. Conclusion: Most studies in different parts of the world have shown that the efficacy of BCG vaccine varies from zero to eigh-ty percent. This study favors the efficacy of BCG vaccine. This vaccination strategy will be favorable for our children. Creation of awareness among the parents and family members for an early administration of BCG vaccine after child birth can be recom-mended.

  9. Passive immunisation, an old idea revisited: Basic principles and application to modern animal production systems

    DEFF Research Database (Denmark)

    Hedegaard, Chris Juul; Heegaard, Peter M. H.

    2016-01-01

    Immunisation by administration of antibodies (immunoglobulins) has been known for more than one hundred years as a very efficient means of obtaining immediate, short-lived protection against infection and/or against the disease-causing effects of toxins from microbial pathogens and from other sou...... development of bacterial resistance, thus constituting a real and widely applicable alternative to antibiotics....... remains big. This review highlights a number of examples on the use of passive immunisation for the control of infectious disease in the modern production of a range of animals, including pigs, cattle, sheep, goat, poultry and fish. Special emphasis is given on the enablement of passive immunisation...... strategies in these production systems through low cost and ease of use as well as on the sources, composition and purity of immunoglobulin preparations used and their benefits as compared to current measures, including vaccination (also comprising maternal vaccination), antibiotics and feed additives...

  10. Social transfer of pathogenic fungus promotes active immunisation in ant colonies.

    Directory of Open Access Journals (Sweden)

    Matthias Konrad

    Full Text Available Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors among group members--that is, active versus passive immunisation. We found no evidence for involvement of passive immunisation via transfer of antimicrobials among colony members. Instead, intensive allogrooming behaviour between naive and pathogen-exposed ants before fungal conidia firmly attached to their cuticle suggested passage of the pathogen from the exposed individuals to their nestmates. By tracing fluorescence-labelled conidia we indeed detected frequent pathogen transfer to the nestmates, where they caused low-level infections as revealed by growth of small numbers of fungal colony forming units from their dissected body content. These infections rarely led to death, but instead promoted an enhanced ability to inhibit fungal growth and an active upregulation of immune genes involved in antifungal defences (defensin and prophenoloxidase, PPO. Contrarily, there was no upregulation of the gene cathepsin L, which is associated with antibacterial and antiviral defences, and we found no increased antibacterial activity of nestmates of fungus-exposed ants. This indicates that social immunisation after fungal exposure is specific, similar to recent findings for individual-level immune priming in invertebrates. Epidemiological modeling further suggests that active social immunisation is adaptive, as it leads to faster elimination of the disease and lower

  11. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis.

    Science.gov (United States)

    Pym, Alexander S; Brodin, Priscille; Majlessi, Laleh; Brosch, Roland; Demangel, Caroline; Williams, Ann; Griffiths, Karen E; Marchal, Gilles; Leclerc, Claude; Cole, Stewart T

    2003-05-01

    The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guérin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (RD1) locus, which is intact in virulent members of the Mycobacterium tuberculosis complex. To increase their immunogenicity and protective capacity, we complemented both vaccines with different constructs containing the esxA and esxB genes, which encode ESAT-6 and CFP-10 respectively, as well as a variable number of flanking genes. Only reintroduction of the complete locus, comprising at least 11 genes, led to full secretion of the antigens and resulted in specific ESAT-6-dependent immune responses; this suggests that the flanking genes encode a secretory apparatus. Mice and guinea pigs vaccinated with the recombinant strain BCG::RD1-2F9 were better protected against challenge with M. tuberculosis, showing less severe pathology and reduced dissemination of the pathogen, as compared with control animals immunized with BCG alone.

  12. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    Science.gov (United States)

    Bacalhau, Sílvia; Freitas, Cristina; Valente, Rosalina; Barata, Deolinda; Neves, Conceição; Schäfer, Katrin; Lubatschofski, Annelie; Schulz, Ansgar; Neves, João Farela

    2011-01-01

    In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highlighting the specific strategies adopted. PMID:22110512

  13. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Sílvia Bacalhau

    2011-01-01

    Full Text Available In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID who developed disseminated BCG disease, highlighting the specific strategies adopted.

  14. Prosthetic Joint Infection due to Mycobacterium bovis after Intravesical Instillation of Bacillus Calmette-Guerin (BCG

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    Eric Gomez

    2009-01-01

    Full Text Available Intravesical instillation of Bacillus Calmette-Guerin (BCG is a treatment to prevent recurrence of superficial urothelial bladder carcinoma. Complications after bladder instillation of BCG have been reported including locally invasive and systemic infections due to dissemination of Mycobacterium bovis from the bladder. We present an uncommon case and literature review of prosthetic joint infection due to M. bovis after intravesical BCG treatment of bladder cancer.

  15. Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

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    Shanmugalakshmi Sadagopal

    Full Text Available BACKGROUND: In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB. Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli. CONCLUSIONS/SIGNIFICANCE: We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.

  16. Chest wall granuloma associated with BCG vaccination presenting as hot abscess in an immunocompetent infant

    OpenAIRE

    Lee, Hyun Seung; Seo, Kyung Jin; Kim, Jae Jun

    2015-01-01

    Bacillus-Calmette-Gue´rin (BCG) vaccine is a live attenuated vaccine to prevent tuberculosis by cell mediated immune response and is routinely administered early after birth. Although it is considered to be a very safe vaccine, sometimes a variety of complications may develop. Herein we describe a clinically unusual case of chest wall granuloma considered to be induced by BCG, presenting as hot abscess, and developed 7 months after BCG vaccination in an immunocompetent infant. The diagnosis w...

  17. Low Dose BCG Infection as a Model for Macrophage Activation Maintaining Cell Viability

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    Leslie Chávez-Galán

    2016-01-01

    Full Text Available Mycobacterium bovis BCG, the current vaccine against tuberculosis, is ingested by macrophages promoting the development of effector functions including cell death and microbicidal mechanisms. Despite accumulating reports on M. tuberculosis, mechanisms of BCG/macrophage interaction remain relatively undefined. In vivo, few bacilli are sufficient to establish a mycobacterial infection; however, in vitro studies systematically use high mycobacterium doses. In this study, we analyze macrophage/BCG interactions and microenvironment upon infection with low BCG doses and propose an in vitro model to study cell activation without affecting viability. We show that RAW macrophages infected with BCG at MOI 1 activated higher and sustained levels of proinflammatory cytokines and transcription factors while MOI 0.1 was more efficient for early stimulation of IL-1β, MCP-1, and KC. Both BCG infection doses induced iNOS and NO in a dose-dependent manner and maintained nuclear and mitochondrial structures. Microenvironment generated by MOI 1 induced macrophage proliferation but not MOI 0.1 infection. In conclusion, BCG infection at low dose is an efficient in vitro model to study macrophage/BCG interactions that maintains macrophage viability and mitochondrial structures. This represents a novel model that can be applied to BCG research fields including mycobacterial infections, cancer immunotherapy, and prevention of autoimmunity and allergies.

  18. The immunological effects of oral polio vaccine provided with BCG vaccine at birth

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Karkov, Hanne Sophie; Lund, Najaaraq

    2014-01-01

    BACKGROUND: Vaccines may have non-specific effects. An observational study from Guinea-Bissau suggested that oral polio vaccine at birth (OPV0) provided with Bacillus Calmette-Guérin (BCG) vaccine was associated with down-regulation of the immune response to BCG vaccine 6 weeks later. Based...... BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-α and IFN-γ) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen...

  19. Protective capacity of proteoliposomes from Mycobacterium bovis BCG in a mouse model of tuberculosis

    Science.gov (United States)

    Tirado, Yanely; Puig, Alina; Alvarez, Nadine; Borrero, Reinier; Aguilar, Alicia; Camacho, Frank; Reyes, Fatima; Fernández, Sonsire; Pérez, José Luis; Espinoza, Dulce Mata; Payán, Jorge Alberto Barrios; Sarmiento, María Elena; Norazmi, Mohd-Nor; Hernández-Pando, Rogelio; Acosta, Armando

    2015-01-01

    Tuberculosis (TB) is one of the most important causes of mortality and morbidity due to infectious diseases. BCG, the vaccine in use, is not fully protective against TB. In a previous study, we have shown that proteoliposomes (outer membrane extracts), obtained from BCG (PLBCG) were able to induce humoral immune responses against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLBCG alone or as a booster with BCG, a murine model of progressive pulmonary TB was used. Animals immunized with PLBCG adjuvanted with alum (PLBCG-Al) showed similar protection to that conferred by BCG. The group immunized with PLBCG-Al as a booster to BCG gave superior protection than BCG as evidenced by a reduction of bacterial load in lungs 2 months after infection with Mtb. Animals immunized with BCG, PLBCG-Al and this formulation as a booster of BCG, showed a significant decrease of tissue damage (percentage of pneumonic area/lung) compared with non-immunized animals. These results demonstrate that immunization with PLBCG-Al alone or as a booster to BCG induce appropriate protection against challenge with Mtb in mice and support the future evaluation of PLBCG as a promising vaccine candidate against Mtb. PMID:25671612

  20. Protective capacity of proteoliposomes from Mycobacterium bovis BCG in a mouse model of tuberculosis.

    Science.gov (United States)

    Tirado, Yanely; Puig, Alina; Alvarez, Nadine; Borrero, Reinier; Aguilar, Alicia; Camacho, Frank; Reyes, Fatima; Fernández, Sonsire; Pérez, José Luis; Espinoza, Dulce Mata; Payán, Jorge Alberto Barrios; Sarmiento, María Elena; Norazmi, Mohd-Nor; Hernández-Pando, Rogelio; Acosta, Armando

    2015-01-01

    Tuberculosis (TB) is one of the most important causes of mortality and morbidity due to infectious diseases. BCG, the vaccine in use, is not fully protective against TB. In a previous study, we have shown that proteoliposomes (outer membrane extracts), obtained from BCG (PLBCG) were able to induce humoral immune responses against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLBCG alone or as a booster with BCG, a murine model of progressive pulmonary TB was used. Animals immunized with PLBCG adjuvanted with alum (PLBCG-Al) showed similar protection to that conferred by BCG. The group immunized with PLBCG-Al as a booster to BCG gave superior protection than BCG as evidenced by a reduction of bacterial load in lungs 2 months after infection with Mtb. Animals immunized with BCG, PLBCG-Al and this formulation as a booster of BCG, showed a significant decrease of tissue damage (percentage of pneumonic area/lung) compared with non-immunized animals. These results demonstrate that immunization with PLBCG-Al alone or as a booster to BCG induce appropriate protection against challenge with Mtb in mice and support the future evaluation of PLBCG as a promising vaccine candidate against Mtb.

  1. Vacina BCG contra tuberculose: efeito protetor e políticas de vacinação BCG vaccine against tuberculosis: its protective effect and vaccination policies

    Directory of Open Access Journals (Sweden)

    Susan M Pereira

    2007-09-01

    Full Text Available OBJETIVO: A vacina BCG é utilizada desde 1921, embora ainda apresente controvérsias e aspectos não esclarecidos. O objetivo do artigo foi analisar aspectos relacionados ao efeito protetor da primeira e segunda doses da vacina BCG e as políticas de vacinação adotadas. MÉTODOS: Foi realizada revisão sistemática da literatura publicada em inglês e espanhol, abrangendo o período compreendido entre 1948 e 2006, na base PubMed. Os principais descritores utilizados foram BCG vaccine, BCG efficacy, BCG e tuberculosis. Os estudos foram agrupados por tipo de desenho, apresentando-se separadamente os principais resultados de ensaios clínicos, estudos de caso-controle e metanálises. RESULTADOS: O efeito protetor da primeira dose da vacina BCG contra a tuberculose na forma miliar ou na meningite é elevado. No entanto, os resultados são discordantes em relação à forma pulmonar, variando de ausência de efeito a níveis próximos a 80%. Estão sendo conduzidas pesquisas sobre novas vacinas candidatas a substituir a BCG ou serem utilizadas como reforço. CONCLUSÕES: Há evidências de que a segunda dose da BCG não aumenta o seu efeito protetor. Apesar de seus limites e da expectativa futura de nova vacina para tuberculose, a vacina BCG mantém-se como importante instrumento no controle dos efeitos danosos da doença, sobretudo em países com taxas de incidência médias e elevadas.OBJECTIVE: The BCG vaccine has been in use since 1921, but still arouses controversy and uncertainties. The objective was to analyze the protective effect of the BCG vaccine in its first and second doses and the accompanying vaccination policies. METHODS: A systematic review of the literature in both English and Spanish was carried out, covering the period 1948 to 2006, using the PubMed database. The main search terms used included BCG vaccine, BCG efficacy, BCG and tuberculosis. The studies were grouped by design, with the main results from the clinic tests, case

  2. We strongly support childhood immunisation-statement from the European Academy of Paediatrics (EAP).

    Science.gov (United States)

    Dornbusch, Hans Juergen; Hadjipanayis, Adamos; Del Torso, Stefano; Mercier, Jean-Christophe; Wyder, Corinne; Schrier, Lenneke; Ross-Russell, Robert; Stiris, Tom; Ludvigsson, Jonas F

    2017-03-10

    The eradication of smallpox and the elimination of several other infectious diseases from much of the world has provided convincing evidence that vaccines are among the most effective interventions for promoting health. The current scepticism about immunisation among members of the new US administration carries a risk of decreasing immunisation rates also in Europe. While only a small minority of the population are strongly anti-vaccine, their public activities have significantly influenced an uncertainty among the general population about both the safety of and the necessity for vaccination. Therefore, the EAP calls for greater publically available, scientifically supported information on vaccination, particularly targeted at health care providers, for the further development of electronically based immunisation information systems (IIS). We further call on all European countries to work together both in legislative and public health arenas in order to increase vaccination coverage among the paediatric population. In the interest of children and their parents, the EAP expresses its strong support for childhood immunisation and recommended vaccination schedules. We are prepared to work with governments and media and share the extensive evidence demonstrating the effectiveness and safety of vaccines.

  3. Risk factors for RhD immunisation despite antenatal and postnatal anti-D prophylaxis

    NARCIS (Netherlands)

    J.M. Koelewijn; M. de Haas; T.G.M. Vrijkotte; C.E. van der Schoot; G.J. Bonsel

    2009-01-01

    Objective To identify risk factors for Rhesus D (RhD) immunisation in pregnancy, despite adequate antenatal and postnatal anti-D prophylaxis in the previous pregnancy. To generate evidence for improved primary prevention by extra administration of anti-D Ig in the presence of a risk factor. Design C

  4. Seroepidemiology of diphtheria, tetanus, poliomyelitis and pertussis : evaluation of the national immunisation programme in the Netherlands

    NARCIS (Netherlands)

    Melker, de H.

    1999-01-01

    In view of the evaluation of the National Immunisation Programme in the Netherlands the main objectives were to obtain insight into the immunity to diphtheria, tetanus and poliomyelitis, into the occurrence of pertussis and to improve serodiagnosis of pertussis.In a population-based nationwide sampl

  5. Pertussis immunisation and control in England and Wales, 1957 to 2012: a historical review.

    Science.gov (United States)

    Amirthalingam, G; Gupta, S; Campbell, H

    2013-09-19

    This review summarises the epidemiology and control of pertussis in England and Wales since the introduction of routine immunisation and considers the implications for future control. Routine infant immunisation with a whole-cell pertussis (wP) vaccine was introduced in 1957 and had a marked impact on the overall disease burden. Following a fall in vaccine coverage during the 1970s and 80s linked to a safety scare with wP vaccine, there was an extended period of high coverage and pertussis incidence fell dramatically. Incidence continued to decrease with the introduction of an acellular pertussis vaccine in the pre-school booster in November 2001 and in the primary United Kingdom (UK) schedule in September 2004 but has increased since July 2011. In response to a high rate of pertussis in infants, a temporary vaccination programme for pregnant women was introduced in October 2012. The key aim of the programme is to protect vulnerable infants from birth in the first months of life, before they can be fully protected by routine infant immunisation. A review of the UK adolescent immunisation programme is currently ongoing and the inclusion of a pertussis booster is being considered.

  6. Shifts in global immunisation goals (1984-2004): unfinished agendas and mixed results

    NARCIS (Netherlands)

    Hardon, A.; Blume, S.

    2005-01-01

    The turn of the millennium has been marked by a large-scale mobilisation of resources for immunisation programmes in developing countries. The resources have been generated by public and private sector parties collaborating in the Global Alliance for Vaccines and Immunization (GAVI). GAVI was formed

  7. Fiscal consequences of changes in morbidity and mortality attributed to rotavirus immunisation

    NARCIS (Netherlands)

    Kotsopoulos, Nikolaos; Connolly, Mark P.; Postma, Maarten J.; Hutubessy, Raymond C.W.

    2013-01-01

    Changes in population health status are known to influence government fiscal transfers both in terms of lost tax revenue and increased expenditure for health and social services. To estimate the fiscal impact of changes in morbidity and mortality attributed to rotavirus immunisation, we developed a

  8. Effects of Edutainment on Knowledge and Perceptions of Lisu Mothers about the Immunisation of Their Children

    Science.gov (United States)

    Dway, Ngwa Sar; Soonthornworasiri, Ngamphol; Jandee, Kasemsak; Lawpoolsri, Saranath; Pan-Ngum, Wirichada; Sinthuvanich, Daorirk; Kaewkungwal, Jaranit

    2016-01-01

    Objective: This study assessed the immediate effects of edutainment modules on changes in knowledge and perceptions towards the Expanded Programme for Immunisation (EPI) among an under served minority (Lisu) population. Method: An edutainment module was developed on mobile tablets for use by village health volunteers. As the study was conducted…

  9. Peripheral blood lymphocyte subsets in Fasciola hepatica infected and immunised goats.

    Science.gov (United States)

    Zafra, R; Pérez, J; Buffoni, L; Martínez-Moreno, F J; Acosta, I; Mozos, E; Martínez-Moreno, A

    2013-09-01

    The proportions of CD4(+), CD8(+) and WC1+ T lymphocytes from peripheral blood using flow cytometry were investigated in goats infected with Fasciola hepatica and previously immunised with recombinant Cathepsin-L1 (rCL1) and Glutathione-S-transferase sigma class (GST). The immunisation trial did not induce protective responses, and no significant differences were recorded between immunised and non-immunised groups. However, there was a significant decrease in the proportion of CD4(+) T lymphocytes in the infected groups both at 5 weeks post-infection (wpi), coinciding with the migratory stage of the infection, and at 12 wpi in the biliary stage of the infection. The proportional decrease in this circulating population may be related to the recruitment of CD4(+) T cells in liver and hepatic lymph nodes and also to the immunomodulatory effect of the parasite through the interaction of F. hepatica excretory-secretory products (FhESP) with this cell population. To date, this is the first report about the effect of F. hepatica infection in peripheral lymphocyte subsets in goats.

  10. Household cost-benefit equations and sustainable universal childhood immunisation: a randomised cluster controlled trial in south Pakistan [ISRCTN12421731

    Directory of Open Access Journals (Sweden)

    Ledogar Robert J

    2005-06-01

    Full Text Available Abstract Background Household decision-makers decide about service use based largely on the costs and perceived benefits of health interventions. Very often this leads to different decisions than those imagined by health planners, resulting in under-utilisation of public services like immunisation. In the case of Lasbela district in the south of Pakistan, only one in every ten children is immunised despite free immunisation offers by government health services. Methods/design In 32 communities representative of Lasbela district, 3344 households participated in a baseline survey on early child health. In the 18 randomly selected intervention communities, we will stimulate discussions on the household cost-benefit equation, as measured in the baseline. The reference (control communities will also participate in the three annual follow-up surveys, feedback of the general survey results and the usual health promotion activities relating to immunisation, but without focussed discussion on the household cost-benefit equations. Discussion This project proposes knowledge translation as a two-way communication that can be augmented by local and international evidence. We will document cultural and contextual barriers to immunisation in the context of household cost-benefit equations. The project makes this information accessible to health managers, and reciprocally, makes information on immunisation effects and side effects available to communities. We will measure the impact of this two-way knowledge translation on immunisation uptake.

  11. Discriminators of mouse bladder response to intravesical Bacillus Calmette-Guerin (BCG

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    Centola Michael

    2007-05-01

    Full Text Available Abstract Background Intravesical Bacillus Calmette-Guerin (BCG is an effective treatment for bladder superficial carcinoma and it is being tested in interstitial cystitis patients, but its precise mechanism of action remains poorly understood. It is not clear whether BCG induces the release of a unique set of cytokines apart from its pro-inflammatory effects. Therefore, we quantified bladder inflammatory responses and alterations in urinary cytokine protein induced by intravesical BCG and compared the results to non-specific pro-inflammatory stimuli (LPS and TNF-α. We went further to determine whether BCG treatment alters cytokine gene expression in the urinary bladder. Methods C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Morphometric analyses were conducted in bladders isolated from all groups and urine was collected for multiplex analysis of 18 cytokines. In addition, chromatin immune precipitation combined with real-time polymerase chain reaction assay (CHIP/Q-PCR was used to test whether intravesical BCG would alter bladder cytokine gene expression. Results Acute BCG instillation induced edema which was progressively replaced by an inflammatory infiltrate, composed primarily of neutrophils, in response to weekly administrations. Our morphological analysis suggests that these polymorphonuclear neutrophils are of prime importance for the bladder responses to BCG. Overall, the inflammation induced by BCG was higher than LPS or TNF-α treatment but the major difference observed was the unique granuloma formation in response to BCG. Among the cytokines measured, this study highlighted the importance of IL-1β, IL-2, IL-3, IL-4, IL-6, IL-10, IL-17, GM-CSF, KC, and Rantes as discriminators between generalized inflammation and BCG-specific inflammatory responses. CHIP/Q-PCR indicates that acute BCG instillation induced an up-regulation of IL-17A, IL-17B, and IL-17RA, whereas chronic BCG induced IL-17B, IL-17RA, and

  12. Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes.

    Science.gov (United States)

    Buddle, Bryce M; Denis, Michel; Aldwell, Frank E; Martin Vordermeier, H; Glyn Hewinson, R; Neil Wedlock, D

    2008-11-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine delivered to calves by the subcutaneous (s.c.) or by the oral route in a formulated lipid matrix has been previously shown to induce similar levels of protection against bovine tuberculosis. The current study was aimed at determining whether a combination of delivering BCG by s.c. and oral routes would enhance levels of protection, compared to only one route of vaccination. Forty calves were randomly divided into four groups (10/group). Calves were vaccinated with 10(6)colony forming units (CFU) of BCG Pasteur by the s.c. route or orally with 10(9)CFU BCG incorporated into a lipid formulation. One group received a combination of BCG administered by both the s.c. and oral routes and a non-vaccinated group served as a control. The two groups of calves that received s.c. BCG produced strong IFN-gamma responses in whole blood cultures stimulated with bovine purified protein derivative (PPD) 3 weeks after vaccination. Cattle vaccinated just with oral BCG in a lipid matrix produced a strong IFN-gamma response 8 weeks after vaccination, and peaking at 11 weeks after vaccination. All calves were challenged by the intratracheal route with M. bovis 15 weeks after vaccination and were euthanized and necropsied to assess protection at 17 weeks following challenge. BCG given s.c. or orally induced significant and comparable levels of protection against the virulent challenge. Vaccination of cattle by a combination of s.c./oral routes did not enhance protection beyond that achieved by s.c. or oral vaccination alone. We conclude that vaccination of cattle with BCG by a combination of routes has no beneficial additive effects, compared to a single s.c. administration of BCG or BCG given orally in a lipid formulation.

  13. Cutaneous complication after BCG vaccination: Case report and review of the literature

    NARCIS (Netherlands)

    Keijsers, R.R.M.C.; Bovenschen, H.J.; Seijger, M.M.B.

    2011-01-01

    Abstract The bacille Calmette-Gu?rin (BCG) vaccination protects against tuberculosis (TB)-related meningitis and disseminated tuberculosis. While severe complications after BCG vaccination are relatively rare, different cutaneous reactions have been reported. We report a patient with a 7-mm erythema

  14. BCG vaccines: their mechanisms of attenuation and impact on safety and protective efficacy.

    Science.gov (United States)

    Liu, Jun; Tran, Vanessa; Leung, Andrea S; Alexander, David C; Zhu, Baoli

    2009-02-01

    Mycobacterium bovis Bacille Calmette-Guérin (BCG) was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, the mechanisms of attenuation of BCG remain poorly understood. BCG is not a single organism, but comprises a number of substrains that differ in genotypes and phenotypes. The impacts of these differences on BCG vaccine properties are largely unknown. Nevertheless, in the past decade, the development of sophisticated genome analysis techniques, coupled with advances in knowledge of the virulence mechanisms of Mycobacterium tuberculosis, have provided greater insights into the attenuation and evolution of BCG. This review article discusses these new developments, focusing on molecular mechanisms that contribute to the attenuation of BCG substrains. It is evident that BCG strains comprise natural mutants of major virulence factors of M. tb, including ESX-1, PDIM/PGL and PhoP, and that BCG substrains differ markedly in virulence level. The impacts of these findings on vaccine properties including adverse reaction effect, tuberculin reactivity and protective efficacy are discussed. These new insights have extremely important implications for national immunization programs and the development of future vaccines.

  15. BCG-mediated bladder cancer immunotherapy: identifying determinants of treatment response using a calibrated mathematical model.

    Science.gov (United States)

    Rentsch, Cyrill A; Biot, Claire; Gsponer, Joël R; Bachmann, Alexander; Albert, Matthew L; Breban, Romulus

    2013-01-01

    Intravesical Bacillus Calmette Guérin (BCG) immunotherapy is considered the standard of care for treatment of non-muscle invasive bladder cancer; however the treatment parameters were established empirically. In order to evaluate potential optimization of clinical parameters of BCG induction therapy, we constructed and queried a new mathematical model. Specifically, we assessed the impact of (1) duration between resection and the first instillation; (2) BCG dose; (3) indwelling time; and (4) treatment interval of induction therapy - using cure rate as the primary endpoint. Based on available clinical and in vitro experimental data, we constructed and parameterized a stochastic mathematical model describing the interactions between BCG, the immune system, the bladder mucosa and tumor cells. The primary endpoint of the model was the probability of tumor extinction following BCG induction therapy in patients with high risk for tumor recurrence. We theoretically demonstrate that extending the duration between the resection and the first BCG instillation negatively influences treatment outcome. Simulations of higher BCG doses and longer indwelling times both improved the probability of tumor extinction. A remarkable finding was that an inter-instillation interval two times longer than the seven-day interval used in the current standard of care would substantially improve treatment outcome. We provide insight into relevant clinical questions using a novel mathematical model of BCG immunotherapy. Our model predicts an altered regimen that may decrease side effects of treatment while improving response to therapy.

  16. Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity

    DEFF Research Database (Denmark)

    Arts, Rob J W; Blok, Bastiaan A; Aaby, Peter

    2015-01-01

    were less strong than those induced by live BCG. γBCG vaccination in volunteers had only minimal effects on innate immunity, whereas a significant increase in heterologous Th1/Th17 immunity was observed. Our results indicate that γBCG induces long-term training of innate immunity in vitro. In vivo, γ...

  17. From compulsory to voluntary immunisation: Italy's National Vaccination Plan (2005-7) and the ethical and organisational challenges facing public health policy-makers across Europe.

    Science.gov (United States)

    Moran, N E; Gainotti, S; Petrini, C

    2008-09-01

    Increasing geographical mobility and international travel augment the ease and speed by which infectious diseases can spread across large distances. It is therefore incumbent upon each state to ensure that immunisation programmes are effective and that herd immunity is achieved. Across Europe, a range of immunisation policies exist: compulsion, the offer of financial incentives to parents or healthcare professionals, social and professional pressure, or simply the dissemination of clear information and advice. Until recently, immunisation against particular communicable diseases was compulsory in Italy. The Italian National Vaccination Plan (NVP) (2005-7) paved the way for regions to suspend the sanctions associated with compulsory vaccinations for children when certain criteria are met--for example when immunisation coverage is high and when effective monitoring/surveillance systems are in place--and thus marked a milestone in the move from compulsory to voluntary immunisation. The forthcoming NVP for 2008-10 confirms the liberal approach to vaccination in Italy as it entrusts to the regions responsibility for the achievement and maintenance of herd immunity. This paper reviews the arguments for and against compulsory and voluntary immunisation in relation to the Italian NVP (2005-7) and in the context of the diverse immunisation policies that exist across Europe. It concludes with cautious support for the NVP and an associated shift from compulsory to voluntary immunisation in Italy, and draws similarities between issues concerning regional variation in immunisation policy in Italy and national variation in immunisation policy across Europe and beyond.

  18. Construction of EGFP-tagged rBCG of E.tenella and distribution in chickens

    Institute of Scientific and Technical Information of China (English)

    WANG QiuYue; LI JianHua; ZHANG XiChen; LIU ChengWu; CAO LiLi; REN KeYan; GONG PengTao; CAI YaNan

    2009-01-01

    Chicken coccidiosis is a major parasitic disease with substantial economic burden to the poultry in-dustry. Enhanced green fluorescent protein (EGFP) tagged recombinant Bacille Calmette-Guerin (rBCG), as a fusion protein with coccidian rhomboid antigen was constructed to track rBCG in vivo in chickens in this study. Immunization of chickens with one dose of rBCG pMV361-Rho/EGFP induced humoral immune response. The colonization of rBCG in liver, spleen, lung, kidney and caecum was observed by laser confocal microscopy. Real-time quantitative RT-PCR showed s rise expression level of rhomboid protein on the 7th day and a peak on the 14th day and disappearance on the 28th day after immunization. These results have significant implications for the development of rBCG vaccines against avian coccidiosis.

  19. Nonspecific effect of BCG vaccination at birth on early childhood infections

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Birk, Nina Marie; Nørrelykke Nissen, Thomas

    2016-01-01

    BackgroundChildhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via non-specific effects.MethodsA randomized, clinical multicenter trial. All women planning to give birth (n = 16521) at the three study sites were invited during the recruitment...... vaccinated. From 3 to 13 months there were 7028 vs. 6791 events, IRR = 1.02 (0.97 to 1.07).ConclusionsThis study did not find a non-specific public health benefit of BCG on parent reported infections. BCG may have reduced the incidence of infections in children of BCG vaccinated mothers during the first 3...... period. Participating children were randomized to receive BCG within seven days of birth or to a no intervention control group. Parent reported infections (events) were collected using telephone interviews at 3 and 13 months. Data collectors were blinded to allocation.ResultsThe analyses included 4224...

  20. Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960.

    Science.gov (United States)

    Brimnes, Niels

    2011-02-01

    Through an examination of mass BCG vaccination against tuberculosis in India between 1948 and 1960 this article draws attention to the diversity of the history of vaccination. The features of vaccination campaigns often differed from those of the celebrated campaign to eradicate smallpox. Due to differences between smallpox and tuberculosis as well as between the vaccines developed against them, an analysis of BCG mass vaccination against tuberculosis seems particularly well suited for this purpose. Three points of difference are identified. First, in non-Western contexts BCG vaccination procedures were modified to a greater extent than vaccination against smallpox. Second, tuberculosis lacked the drama and urgency of smallpox and BCG vaccination campaigns suffered more from recruitment problems than did the more "heroic" smallpox eradication campaign. Third, the BCG vaccine was contested in medical circles and was much better suited than the vaccine against smallpox as a vehicle for the articulation of concerns about post-colonial modernization.

  1. Adverse effects of BCG vaccine 1173 P2 in Iran: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Saied Mostaan

    2016-01-01

    Full Text Available Although in the last two decades the World Health Organization (WHO has introduced tuberculosis as “a threat to global”, the vaccination with the Mycobacterium bovis Bacillus Calmette-Guerin (BCG is the only way for the prevention of this fatal infectious disease. Despite of the efficacy of BCG vaccine especially against infants' meningitis, it has still some limitations due to a variety of adverse effects. Many studies have evaluated the side effects of different strains of BCG vaccines in different countries. In Iran, some studies have been done so far to evaluate the adverse effects of 1173 P2 strain which is used for BCG vaccination. Each of these studies have used different standardization and sampling methods. This review will survey all studies that have been published about adverse effects of 1173 P2 strain of BCG vaccine in Iran using data mining methods.

  2. Adverse effects of BCG vaccine 1173 P2 in Iran: A meta-analysis

    Science.gov (United States)

    Mostaan, Saied; Yazdanpanah, Bahador; Moukhah, Rasool; Hozouri, Hamid Reza; Rostami, Manouchehr; Khorashadizadeh, Mohsen; Zerehsaz, Javad; Mahabadi, Ramin Pirhajati; Saadi, Arya; Khanahmad, Hossein; Pooya, Mohammad

    2016-01-01

    Although in the last two decades the World Health Organization (WHO) has introduced tuberculosis as “a threat to global”, the vaccination with the Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the only way for the prevention of this fatal infectious disease. Despite of the efficacy of BCG vaccine especially against infants’ meningitis, it has still some limitations due to a variety of adverse effects. Many studies have evaluated the side effects of different strains of BCG vaccines in different countries. In Iran, some studies have been done so far to evaluate the adverse effects of 1173 P2 strain which is used for BCG vaccination. Each of these studies have used different standardization and sampling methods. This review will survey all studies that have been published about adverse effects of 1173 P2 strain of BCG vaccine in Iran using data mining methods. PMID:27376038

  3. Construction of EGFP-tagged rBCG of E.tenella and distribution in chickens

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Chicken coccidiosis is a major parasitic disease with substantial economic burden to the poultry industry.Enhanced green fluorescent protein(EGFP) tagged recombinant Bacille Calmette-Guerin(rBCG),as a fusion protein with coccidian rhomboid antigen was constructed to track rBCG in vivo in chickens in this study.Immunization of chickens with one dose of rBCG pMV361-Rho/EGFP induced humoral immune response.The colonization of rBCG in liver,spleen,lung,kidney and caecum was observed by laser confocal microscopy.Real-time quantitative RT-PCR showed a rise expression level of rhomboid protein on the 7th day and a peak on the 14th day and disappearance on the 28th day after immunization.These results have significant implications for the development of rBCG vaccines against avian coccidiosis.

  4. Chest wall granuloma associated with BCG vaccination presenting as hot abscess in an immunocompetent infant.

    Science.gov (United States)

    Lee, Hyun Seung; Seo, Kyung Jin; Kim, Jae Jun

    2015-03-04

    Bacillus-Calmette-Gue´rin (BCG) vaccine is a live attenuated vaccine to prevent tuberculosis by cell mediated immune response and is routinely administered early after birth. Although it is considered to be a very safe vaccine, sometimes a variety of complications may develop. Herein we describe a clinically unusual case of chest wall granuloma considered to be induced by BCG, presenting as hot abscess, and developed 7 months after BCG vaccination in an immunocompetent infant. The diagnosis was made based on the history, histopathology and virological studies. We suggest, although very rare, a BCG disease should be considered as a differential diagnosis in case of chest wall abscess, even if this is presenting as a hot abscess and even in immunocompetent infants if their age is related to BCG vaccination complications.

  5. Pre-clinical development of BCG.HIVA(CAT, an antibiotic-free selection strain, for HIV-TB pediatric vaccine vectored by lysine auxotroph of BCG.

    Directory of Open Access Journals (Sweden)

    Narcís Saubi

    Full Text Available In the past, we proposed to develop a heterologous recombinant BCG prime-recombinant modified vaccinia virus Ankara (MVA boost dual pediatric vaccine platform against transmission of breast milk HIV-1 and Mycobacterium tuberculosis (Mtb. In this study, we assembled an E. coli-mycobacterial shuttle plasmid pJH222.HIVA(CAT expressing HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism based on Operator-Repressor Titration (ORT system for plasmid selection and maintenance in E. coli and lysine complementation in mycobacteria. This shuttle plasmid was electroporated into parental lysine auxotroph (safer strain of BCG to generate vaccine BCG.HIVA(CAT. All procedures complied with Good Laboratory Practices (GLPs. We demonstrated that the episomal plasmid pJH222.HIVA(CAT was stable in vivo over a 20-week period, and genetically and phenotypically characterized the BCG.HIVA(CAT vaccine strain. The BCG.HIVA(CAT vaccine in combination with MVA.HIVA induced HIV-1- and Mtb-specific interferon γ-producing T-cell responses in newborn and adult BALB/c mice. On the other hand, when adult mice were primed with BCG.HIVA(CAT and boosted with MVA.HIVA.85A, HIV-1-specific CD8(+ T-cells producing IFN-γ, TNF-α, IL-2 and CD107a were induced. To assess the biosafety profile of BCG.HIVA(CAT-MVA.HIVA regimen, body mass loss of newborn mice was monitored regularly throughout the vaccination experiment and no difference was observed between the vaccinated and naïve groups of animals. Thus, we demonstrated T-cell immunogenicity of a novel, safer, GLP-compatible BCG-vectored vaccine using prototype immunogen HIVA. Second generation immunogens derived from HIV-1 as well as other major pediatric pathogens can be constructed in a similar fashion to prime protective responses soon after birth.

  6. BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Hermann Inge-Marie

    2010-06-01

    Full Text Available Abstract Background Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC. We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines. Results In contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4-Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip. Conclusions S4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC.

  7. Status of maternal care and immunisation services in a hilly state of north India: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Anupam Parashar

    2016-08-01

    Conclusions: Overall, the utilisation of maternal health services and immunisation against maternal and neonatal Tetanus are excellent in the state. The coverage targets for key RMNCH and A, an interventions have been well achieved in the state. Further, sustained efforts with Supportive Supervision are required to achieve 100% universal coverage of immunisation and full utilisation of maternal health care services. [Int J Reprod Contracept Obstet Gynecol 2016; 5(8.000: 2607-2611

  8. Preparation and stability of agarose microcapsules containing BCG.

    Science.gov (United States)

    Esquisabel, A; Hernandez, R M; Igartua, M; Gascón, A R; Calvo, B; Pedraz, J L

    2002-01-01

    An emulsification/internal gelation method of preparing small-sized agarose microcapsules containing Bacillus Calmette-Guerin (BCG) is reported. Agarose microcapsules have been prepared by the emulsification of the hydrogel within a vegetable oil followed by its gelation due to the cooling of the system. Four different oils (sesame, sweet almonds, camomile and jojoba) were assayed. The rheological analysis of the oils showed a Newtonian behaviour, with viscosity values of 37.7, 51.2, 59.3 and 67.1 mPa s for jojoba, camomile, sesame and sweet almonds oil, respectively. The particle size of the microcapsules obtained ranged from 23.1 microm for the microcapsules prepared with sweet almonds oil to 42.6 microm for those prepared with jojoba. The microcapsule particle size was found to be dependent on the viscosity of the oil used in the emulsification step. The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Once prepared, microcapsules were freeze-dried using 5% trehalose as cryoprotectant and the stability of the microcapsules was assayed during 12 months storage at room temperature, observing that agarose microcapsules were stable after 12 months storage, since there was no evidence of alteration in the freeze-dried appearance, resuspension rate, observation under microscope, or particle size.

  9. Cosmological Constraints from the SDSS maxBCG Cluster Catalog

    Energy Technology Data Exchange (ETDEWEB)

    Rozo, Eduardo; /CCAPP; Wechsler, Risa H.; /KIPAC, Menlo Park /SLAC; Rykoff, Eli S.; /UC, Santa Barbara; Annis, James T.; /Fermilab; Becker, Matthew R.; /Chicago U. /KICP, Chicago; Evrard, August E.; /Michigan U. /Michigan U., MCTP; Frieman, Joshua A.; /Fermilab /KICP, Chicago /Chicago U.; Hansen, Sarah M.; /UC, Santa Cruz; Hao, Jia; /Michigan U.; Johnston, David E.; /Northwestern U.; Koester, Benjamin P.; /KICP, Chicago /Chicago U.; McKay, Timothy A.; /Michigan U. /Michigan U., MCTP; Sheldon, Erin S.; /Brookhaven; Weinberg, David H.; /CCAPP /Ohio State U.

    2009-08-03

    We use the abundance and weak lensing mass measurements of the SDSS maxBCG cluster catalog to simultaneously constrain cosmology and the richness-mass relation of the clusters. Assuming a flat {Lambda}CDM cosmology, we find {sigma}{sub 8}({Omega}{sub m}/0.25){sup 0.41} = 0.832 {+-} 0.033 after marginalization over all systematics. In common with previous studies, our error budget is dominated by systematic uncertainties, the primary two being the absolute mass scale of the weak lensing masses of the maxBCG clusters, and uncertainty in the scatter of the richness-mass relation. Our constraints are fully consistent with the WMAP five-year data, and in a joint analysis we find {sigma}{sub 8} = 0.807 {+-} 0.020 and {Omega}{sub m} = 0.265 {+-} 0.016, an improvement of nearly a factor of two relative to WMAP5 alone. Our results are also in excellent agreement with and comparable in precision to the latest cosmological constraints from X-ray cluster abundances. The remarkable consistency among these results demonstrates that cluster abundance constraints are not only tight but also robust, and highlight the power of optically-selected cluster samples to produce precision constraints on cosmological parameters.

  10. Cosmological Constraints From SDSS MaxBCG Cluster Abundances

    Energy Technology Data Exchange (ETDEWEB)

    Rozo, Eduardo; /Ohio State U. /Chicago U. /KICP, Chicago; Wechsler, Risa H.; /KICP, Chicago /KIPAC, Menlo Park; Koester, Benjamin P.; /Chicago U., Astron. Astrophys. Ctr.; McKay, Timothy A.; Evrard, August E.; /Michigan U.; Johnston, David; /Caltech, JPL; Sheldon, Erin S.; /CCPP, New York; Annis, James; /Fermilab; Frieman, Joshua A.; /KICP,

    2007-03-26

    We perform a maximum likelihood analysis of the cluster abundance measured in the SDSS using the maxBCG cluster finding algorithm. Our analysis is aimed at constraining the power spectrum normalization {sigma}{sub 8}, and assumes flat cosmologies with a scale invariant spectrum, massless neutrinos, and CMB and supernova priors {Omega}{sub m}h{sup 2} = 0.128 {+-} 0.01 and h = 0.72 {+-} 0.05 respectively. Following the method described in the companion paper Rozo et al. (2007), we derive {sigma}{sub 8} = 0.92 {+-} 0.10 (1{sigma}) after marginalizing over all major systematic uncertainties. We place strong lower limits on the normalization, {sigma}{sub 8} > 0.76 (95% CL) (> 0.68 at 99% CL). We also find that our analysis favors relatively low values for the slope of the Halo Occupation Distribution (HOD), {alpha} = 0.83 {+-} 0.06. The uncertainties of these determinations will substantially improve upon completion of an ongoing campaign to estimate dynamical, weak lensing, and X-ray cluster masses in the SDSS maxBCG cluster sample.

  11. Hepatoprotective role of ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    Guo-Liang Zhang; Ye-Hong Wang; Wei Ni; Hui-Ling Teng; Zhi-Bin Lin

    2002-01-01

    AIM: To examine the effect of ganoderma lucidumpolysaccharide (GLP) on the immune liver injuryinduced by BCG infection, and investigate therelationship between degrees of hepatic damage andNO production in mice.METHODS: Immune hepatic injury was markedlyinduced by BCG-pretreatment (125 mg.kg-1, 2-week, iv)or by BCG-pretreatment plus lipopolysaccharide (LPS,125 μg.kg-1, 12-hour, iv) in mice in vivo.Hepatocellulardamage induced by BCG-pretreated plus inflammatorycytokines mixture (CM), which was included TNF-α, IL1β, IFN-γ and LPS in culture medium in vitro.Administration of GLP was performed by oral orincubating with culture medium at immune stimulisimultaneity. Liver damage was determined by activityof alanine aminotransferase (ALT) in serum and inhepatocytes cultured supernatant, by liver weightchanges and histopathological examination. NOproduction in the cultured supematant was determinedby the Griess reaction. Moreover, inducible nitric oxidesynthase (iNOS) protein expression was alsoexaminated by immunohistochemi1cal method.RESULTS: Immune hepatic injury was markedly inducedby BCG or BCG plus inflammatory cytokines in BALB/cmice in vivoand in vitro. Under BCG-stimulated condition,augment of the liver weight and increase of the serum/supernatant ALT level were observed, as well asgranuloma forming and inflammatory cells soakage wereobserved by microscopic analysis within liver tissues.Moreover, NO production was also increased by BCG or/and CH stimuli in the culture supernatant, and a lot ofiNOS positive staining was observed in BCG-prestimulated hepatic sections. Application of GLPsignificantly mitigated hepatic tumefaction, decreasedALT enzyme release and NO production in serum/supernatant, improved the pathological changes ofchronic and acute inflammation induced by BCG-stimuliin mice. Moreover, the immunohistochemical resultshowed that GLP inhibited iNOS protein expression inBCG-immune hepatic damage model.CONCLUSION: The present study indicates that

  12. Designing the Expanded Programme on Immunisation (EPI) as a service: Prioritising patients over administrative logic

    DEFF Research Database (Denmark)

    McKnight, J.; Holt, D. B.

    2014-01-01

    Expanded Programme on Immunisation (EPI) vaccination rates remain well below herd immunity in regions of many countries despite huge international resources devoted to both financing and access. We draw upon service marketing theory, organisational sociology, development anthropology and cultural...... specific service problems from the mother's perspective and points towards simple service innovations that could improve vaccination rates in regions that have poor uptake.......Expanded Programme on Immunisation (EPI) vaccination rates remain well below herd immunity in regions of many countries despite huge international resources devoted to both financing and access. We draw upon service marketing theory, organisational sociology, development anthropology and cultural......-the-ground problems that mothers face in trying to vaccinate their children, while instead prioritising administrative processes. Our ethnographic analysis of 83 mothers who had not vaccinated their children reveals key barriers to vaccination from a 'customer' perspective. While mothers value vaccination...

  13. Protection against avian necrotic enteritis after immunisation with NetB genetic or formaldehyde toxoids.

    Science.gov (United States)

    Fernandes da Costa, Sérgio P; Mot, Dorien; Bokori-Brown, Monika; Savva, Christos G; Basak, Ajit K; Van Immerseel, Filip; Titball, Richard W

    2013-08-20

    NetB (necrotic enteritis toxin B) is a recently identified β-pore-forming toxin produced by Clostridium perfringens. This toxin has been shown to play a major role in avian necrotic enteritis. In recent years, a dramatic increase in necrotic enteritis has been observed, especially in countries where the use of antimicrobial growth promoters in animal feedstuffs has been banned. The aim of this work was to determine whether immunisation with a NetB toxoid would provide protection against necrotic enteritis. The immunisation of poultry with a formaldehyde NetB toxoid or with a NetB genetic toxoid (W262A) resulted in the induction of antibody responses against NetB and provided partial protection against disease.

  14. Need for Optimisation of Immunisation Strategies Targeting Invasive Meningococcal Disease in the Netherlands

    Directory of Open Access Journals (Sweden)

    Josefien Cornelie Minthe Bousema

    2015-11-01

    Full Text Available Invasive meningococcal disease (IMD is a severe bacterial infectious disease with high mortality and morbidity rates worldwide. In recent years, industrialised countries have implemented vaccines targeting IMD in their National Immunisation Programmes (NIPs. In 2002, the Netherlands successfully implemented a single dose of meningococcal serogroup C conjugate vaccine at the age of 14 months and performed a single catch-up for children ≤18 years of age. Since then the disease disappeared in vaccinated individuals. Furthermore, herd protection was induced, leading to a significant IMD reduction in non-vaccinated individuals. However, previous studies revealed that the current programmatic immunisation strategy was insufficient to protect the population in the foreseeable future. In addition, vaccines that provide protection against additional serogroups are now available. This paper describes to what extent the current strategy to prevent IMD in the Netherlands is still sufficient, taking into account the burden of disease and the latest scientific knowledge related to IMD and its prevention. In particular, primary MenC immunisation seems not to provide long-term protection, indicating a risk for possible recurrence of the disease. This can be combatted by implementing a MenC or MenACWY adolescent booster vaccine. Additional health benefits can be achieved by replacing the primary MenC by a MenACWY vaccine. By implementation of a recently licensed MenB vaccine for infants in the NIP, the greatest burden of disease would be targeted. This paper shows that optimisation of the immunisation strategy targeting IMD in the Netherlands should be considered and contributes to create awareness concerning prevention optimisation in other countries.

  15. Need for Optimisation of Immunisation Strategies Targeting Invasive Meningococcal Disease in the Netherlands.

    Science.gov (United States)

    Bousema, Josefien Cornelie Minthe; Ruitenberg, Joost

    2015-09-13

    Invasive meningococcal disease (IMD) is a severe bacterial infectious disease with high mortality and morbidity rates worldwide. In recent years, industrialised countries have implemented vaccines targeting IMD in their National Immunisation Programmes (NIPs). In 2002, the Netherlands successfully implemented a single dose of meningococcal serogroup C conjugate vaccine at the age of 14 months and performed a single catch-up for children ≤18 years of age. Since then the disease disappeared in vaccinated individuals. Furthermore, herd protection was induced, leading to a significant IMD reduction in non-vaccinated individuals. However, previous studies revealed that the current programmatic immunisation strategy was insufficient to protect the population in the foreseeable future. In addition, vaccines that provide protection against additional serogroups are now available. This paper describes to what extent the current strategy to prevent IMD in the Netherlands is still sufficient, taking into account the burden of disease and the latest scientific knowledge related to IMD and its prevention. In particular, primary MenC immunisation seems not to provide long-term protection, indicating a risk for possible recurrence of the disease. This can be combatted by implementing a MenC or MenACWY adolescent booster vaccine. Additional health benefits can be achieved by replacing the primary MenC by a MenACWY vaccine. By implementation of a recently licensed MenB vaccine for infants in the NIP, the greatest burden of disease would be targeted. This paper shows that optimisation of the immunisation strategy targeting IMD in the Netherlands should be considered and contributes to create awareness concerning prevention optimisation in other countries.

  16. Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial

    DEFF Research Database (Denmark)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Smits, Gaby

    2017-01-01

    INTRODUCTION: BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG......) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. METHODS: Within 7days after birth, children were randomised 1:1 to BCG vaccination...... children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis...

  17. Early BCG vaccine to low-birth-weight infants and the effects on growth in the first year of life

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Andersen, Andreas; Ravn, Henrik

    2015-01-01

    BACKGROUND: Randomised trials have shown that early Bacille Calmette-Guérin (BCG) vaccine reduces overall neonatal and infant mortality. However, no study has examined how BCG affects growth. We investigated the effect on infant growth of early BCG vaccine given to low-birth-weight (LBW) infants....... METHODS: Two-thousand three hundred forty-three LBW infants were randomly allocated 1:1 to "early BCG" (intervention group) or "late BCG" (current practice). Furthermore, a subgroup (N = 1717) were included in a two-by-two randomised trial in which they were additionally randomised 1:1 to vitamin...... but not among boys (interaction between "early BCG" and sex: weight p = 0.03 and MUAC p = 0.04). This beneficial effect among girls was particularly seen among the largest infants weighing 2.0 kg or more at inclusion. CONCLUSION: Though BCG vaccination is not recommended to be given to LBW infants at birth...

  18. Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils

    Science.gov (United States)

    Tovar, Cesar; Pye, Ruth J.; Kreiss, Alexandre; Cheng, Yuanyuan; Brown, Gabriella K.; Darby, Jocelyn; Malley, Roslyn C.; Siddle, Hannah V. T.; Skjødt, Karsten; Kaufman, Jim; Silva, Anabel; Baz Morelli, Adriana; Papenfuss, Anthony T.; Corcoran, Lynn M.; Murphy, James M.; Pearse, Martin J.; Belov, Katherine; Lyons, A. Bruce; Woods, Gregory M.

    2017-01-01

    Devil facial tumour disease (DFTD) is a transmissible cancer devastating the Tasmanian devil (Sarcophilus harrisii) population. The cancer cell is the ‘infectious’ agent transmitted as an allograft by biting. Animals usually die within a few months with no evidence of antibody or immune cell responses against the DFTD allograft. This lack of anti-tumour immunity is attributed to an absence of cell surface major histocompatibility complex (MHC)-I molecule expression. While the endangerment of the devil population precludes experimentation on large experimental groups, those examined in our study indicated that immunisation and immunotherapy with DFTD cells expressing surface MHC-I corresponded with effective anti-tumour responses. Tumour engraftment did not occur in one of the five immunised Tasmanian devils, and regression followed therapy of experimentally induced DFTD tumours in three Tasmanian devils. Regression correlated with immune cell infiltration and antibody responses against DFTD cells. These data support the concept that immunisation of devils with DFTD cancer cells can successfully induce humoral responses against DFTD and trigger immune-mediated regression of established tumours. Our findings support the feasibility of a protective DFTD vaccine and ultimately the preservation of the species. PMID:28276463

  19. Immunisation with recombinant proteins subolesin and Bm86 for the control of Dermanyssus gallinae in poultry.

    Science.gov (United States)

    Harrington, David; Canales, Mario; de la Fuente, José; de Luna, Carlos; Robinson, Karen; Guy, Jonathan; Sparagano, Olivier

    2009-06-19

    Dermanyssus gallinae has a worldwide distribution and is considered to be the most serious and economically significant ectoparasite affecting egg-laying poultry in Europe. Recombinant Bm86 and subolesin proteins derived from Boophilus microplus ticks and Aedes albopictus mosquitoes were used to immunise poultry in an attempt to control D. gallinaein vitro. Immunisation with subolesin and Bm86 stimulated different profiles of IgY response, whilst Bm86 but not subolesin was recognized by IgY on western blots. Orthologues for Bm86 were not found in D. gallinae by PCR, but a 150 bp fragment aligned with mammalian akirin 1 and a 300 bp fragment aligned with Amblyomma hebraeum were amplified by subolesin PCR. D. gallinae mortality after feeding was 35.1% higher (P=0.009) in the Subolesin group and 23% higher (not significant) in the Bm86 compared to the Control group. Thus it can be concluded that immunisation with recombinant subolesin can stimulate a protective response in laying hens against D. gallinae.

  20. Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment

    DEFF Research Database (Denmark)

    Sartono, E.; Lisse, I.M.; Terveer, E.M.

    2010-01-01

    Background: Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did...... not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. Methods and Findings: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG...... scar (0.95 (0.91-1.00), p = 0.057)). Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being -0.24 (-0.43-0.05), p = 0.012. Conclusions: This study is the first to address the consequences for the immune response to BCG of simultaneous administration...

  1. Nanoparticulation of BCG-CWS for application to bladder cancer therapy.

    Science.gov (United States)

    Nakamura, Takashi; Fukiage, Masafumi; Higuchi, Megumi; Nakaya, Akihiro; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Ito, Toshihiro; Hosokawa, Hiroyuki; Nakayama, Toshinori; Harashima, Hideyoshi

    2014-02-28

    The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166nm-sized lipid particles. The BCG-CWS encapsulated nano particle (CWS-NP) has a high uniformity and can be easily dispersed. Thus, it has the potential for use as a packaging method that would advance the scope of applications of BCG-CWS as a bladder cancer drug. In a functional evaluation, CWS-NP was efficiently taken up by mouse bladder tumor (MBT-2) cells in vitro and inhibited tumor growth in mice bearing MBT-2 tumors. Moreover, intravesically administered CWS-NP showed significant antitumor effects in a rat model with naturally developed bladder cancer. An enhancement in Th1 differentiation by CWS-NP was also confirmed in human T cells. In conclusion, CWS-NP represents a promising delivery system for BCG-CWS for clinical development as a potent bladder cancer drug.

  2. The BCG Moreau RD16 deletion inactivates a repressor reshaping transcription of an adjacent gene.

    Science.gov (United States)

    Galvão, Teca Calcagno; Lima, Cristiane Rodrigues; Gomes, Leonardo Henrique Ferreira; Pagani, Talita Duarte; Ferreira, Marcelo Alves; Gonçalves, Antonio S; Correa, Paloma Rezende; Degrave, Wim Maurits; Mendonça-Lima, Leila

    2014-01-01

    The Brazilian anti-tuberculosis vaccine strain Mycobacterium bovis bacillus Calmette-Guérin (BCG) BCG Moreau is unique in having a deletion of 7608 bp (RD16) that results in the truncation of a putative TetR transcriptional regulator, the ortholog of Mycobacterium tuberculosis rv3405c, BCG_M3439c. We investigated the effect of this truncation on the expression of the rv3406 ortholog (BCG_M3440), lying 81 bp downstream in the opposite orientation. RT-PCR and western blot experiments show that rv3406 mRNA and Rv3406 accumulate in BCG Moreau but not in BCG Pasteur (strain that bears an intact rv3405c), suggesting this to be a result of rv3405c truncation. Recombinant Rv3405c forms a complex with the rv3405c-rv3406 intergenic region, which contains a characteristic transcription factor binding site, showing it to have DNA binding activity. Complementation of M. bovis BCG Moreau with an intact copy of rv3405c abolishes Rv3406 accumulation. These results show that Rv3405c is a DNA binding protein that acts as a transcriptional repressor of rv3406.

  3. Active Mycobacterium Infection Due to Intramuscular BCG Administration Following Multi-Steps Medication Errors

    Directory of Open Access Journals (Sweden)

    MohammadReza Rafati

    2015-10-01

    Full Text Available Bacillus Calmette-Guérin (BCG is indicated for treatment of primary or relapsing flat urothelial cell carcinoma in situ (CIS of the urinary bladder. Disseminated infectious complications occasionally occur due to BCG as a vaccine and intravesical therapy.  Intramuscular (IM or Intravenous (IV administrations of BCG are rare medication errors which are more probable to produce systemic infections. This report presents 13 years old case that several steps medication errors occurred consequently from physician handwriting, pharmacy dispensing, nursing administration and patient family. The physician wrote βHCG instead of HCG in the prescription. βHCG was read as BCG by the pharmacy staff and 6 vials of intravesical BCG were administered IM twice a week for 3 consecutive weeks. The patient experienced fever and chills after each injection, but he was admitted 2 months after first IM administration of BCG with fever and pancytopenia. Unfortunately four month after using drug, during second admission duo to cellulitis at the sites of BCG injection the physicians diagnosed the medication error. Using handwritten prescription and inappropriate abbreviations, spending inadequate time for taking a brief medical history in pharmacy, lack of verifying name, dose and wrote before medication administration and lack of considering medication error as an important differential diagnosis had roles to occur this multi-steps medication error.

  4. Novel intravesical therapies for non-muscle-invasive bladder cancer refractory to BCG.

    Science.gov (United States)

    Barlow, Lamont J; Seager, Catherine M; Benson, Mitchell C; McKiernan, James M

    2010-01-01

    The definitive treatment for patients with non-muscle-invasive bladder cancer (NMIBC) who fail to respond to intravesical BCG is cystectomy. When a patient is deemed BCG-refractory and cannot or will not undergo cystectomy, alternative intravesical therapy may be the most effective way to minimize recurrence and progression. A number of immunotherapeutic and chemotherapeutic agents have been given intravesically over the years, and several recently and currently investigated novel agents appear to be particularly promising for the management of BCG-refractory NMIBC. The most effective treatments in the future will likely utilize targeted therapies based on the underlying genetic mutations associated with each individual diagnosis of NMIBC.

  5. "A Study of Relation between BCG Scar and Atopy in Schoolchildren of Zanjan City "

    Directory of Open Access Journals (Sweden)

    Akefeh Ahmadiafshar

    2005-12-01

    Three hundred and three subjects had at least one of these disorders, which were diagnosed as atopy. There was reverse correlation between BCG scar and asthma (P=0.013, atopic dermatitis (P<0.01, and atopy (P<0.01. We did not find any association between the diameter of BCG scar and allergic rhinitis. Reverse correlation of asthma, atopic dermatitis and atopy with BCG scar are significant. This relied on history and symptoms of patients. Further studies with skin tests, measurements of total and specific IgE levels and spirometery are recommended.

  6. BCG plus levamisole following irradiation of advanced squamous bronchial carcinoma. [Hard X Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pines, A.

    1980-08-01

    Fifty patients with inoperable squamous cell carcinoma of the bronchus were treated with radical radiotherapy. Afterwards, 16 patients received levamisole on 2 days per week and bacillus calmette guerin (B.C.G.) skin innoculations every two weeks;another 16 received the same dosage of levamisole but B.C.G. every 4 weeks; 18 patients were controls. Survival was better in the first group of patients only during the first two years of study (P = 0.02) but not later: metastases were fewer. Both B.C.G. and levamisole gave little discomfort when the dose was adjusted for each patient.

  7. A COMBINED FULL-WAVE BCG-FFT METHOD FOR RADIATION OF MICROSTRIP ANTENNA ARRAYS

    Institute of Scientific and Technical Information of China (English)

    Zhang Hou; Peng Hongli; Liu Qizhong; Yin Yingzeng; Gong Shuxi

    2001-01-01

    A method of combining BiConjugate Gradient(BCG) with Fast Fourier Transform(FFT) to analyze the radiation of microstrip antenna arrays is presented, where the spatially discrete BCG-FFT for analyzing microstrip structure is used and the del operators on Green's functions are transferred from the singular kernel to the expansion and testing functions. The resultant equations are solved by using BCG method in which the matrix-vector product is evaluated efficiently with FFT. The calculated patterns are in good agreement with the measured data.

  8. Oral vaccination with lipid-formulated BCG induces a long-lived, multifunctional CD4(+ T cell memory immune response.

    Directory of Open Access Journals (Sweden)

    Lindsay R Ancelet

    Full Text Available Oral delivery of BCG in a lipid formulation (Liporale™-BCG targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4(+ T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4(+ T cell response, evident by the detection of effector CD4(+ T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4(+ T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4(+ T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4(+ T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines.

  9. rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

    Science.gov (United States)

    Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

    2014-09-01

    Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy.

  10. Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood

    DEFF Research Database (Denmark)

    Kiraly, N; Benn, Christine Stabell; Biering-Sørensen, S

    2013-01-01

    Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood....

  11. How do parents make their decision about letting their child get a BCG vaccination?

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte; Ammentorp, Jette; Schmidt Jensen, Jane

    Introduction: In a large prospective randomised clinical trial in Denmark we are testing the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood. My...... focus for this project is parents decision making and risk evaluation. I want to investigate how parents make their decision about letting their child get a BCG vaccination and how they evaluate the risk of side effects. Method: Before the clinical trial was started, we conducted 5 focus groups...... with expectant mothers and fathers to discuss considerations for and against letting their newborn child vaccinate with BCG in order to achieve a non-specific stimulation of the immune system and to discuss their concerns about side effects. The focus groups were analysed qualitatively. Results: The pre...

  12. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, A.E.; Benn, Christine Stabell; Ravn, H.;

    2010-01-01

    children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrolment (hazard...... inhabitants. Participants 2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrolment. Intervention BCG vaccination or no vaccination (control). Main outcome measure Hazard ratios for mortality. Results 77 children died during follow...... controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated...

  13. Comparison of BCG vaccination at birth and at third month of life.

    Science.gov (United States)

    Ildirim, I; Sapan, N; Cavuşoğlu, B

    1992-01-01

    Tuberculosis is an important health problem in developing countries and the BCG vaccine plays an important part in preventing the disease. There are different reports about the preventive value of BCG. Some of them claim that it is satisfactory while others suggest that it provides little protection. There are also varying ideas about the optimum time to vaccinate babies, some studies suggesting that late vaccination confers a high degree of protection. This prospective controlled study has been undertaken to evaluate the value of BCG vaccine given to babies during their first three days of life versus its value when given in their third month of life. Evaluation was measured by the results of tests with purified protein derivative (PPD), by vaccine scars, that by the complications of the vaccine. It was found that BCG given at the end of the third month provides a higher rate of response and fewer complications than when given during the first three days of life.

  14. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Fisker, Ane Baerent; Napirna, Bitiguida Mutna

    2010-01-01

    OBJECTIVE: To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates. DESIGN: Randomised, placebo controlled, two by two factorial trial. SETTING: Bissau, Guinea-Bissau. PARTICIPANTS: 1717 low birthweight neonates born at the national hospital....... INTERVENTION: Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12 months. MAIN OUTCOME MEASURE: Mortality, calculated as mortality rate ratios (MRRs), after follow-up to 12...... months of age for infants who received vitamin A supplementation compared with those who received placebo. RESULTS: No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality...

  15. Role of a bacillus Calmette-Guérin fibronectin attachment protein in BCG-induced antitumor activity.

    Science.gov (United States)

    Zhao, W; Schorey, J S; Bong-Mastek, M; Ritchey, J; Brown, E J; Ratliff, T L

    2000-04-01

    Intravesical Mycobacterium bovis bacillus Calmette-Gu*erin (BCG) is the treatment of choice for superficial bladder cancer. Previous studies showed that attachment of BCG to fibronectin within the bladder was necessary for mediation of the antitumor response. Further studies identified a bacterial receptor, fibronectin attachment protein (FAP), as an important mediator of BCG attachment to fibronectin. In vitro studies showed that a stable BCG/fibronectin interaction was dependent on FAP binding to fibronectin; however, no role for FAP in the attachment of BCG in vivo has been characterized. We now report the cloning of the M. bovis BCG FAP (FAP-B) and demonstrate an important role for FAP in the in vivo attachment of BCG to the bladder wall and in the induction of BCG-mediated antitumor activity. The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L). Rabbit polyclonal antibodies against Mycobacterium vaccae FAP (FAP-V) reacted with all 3 recombinant FAP proteins on Western blots. Functional studies show FAP-B to bind fibronectin via the highly conserved attachment regions previously identified for FAP-A and FAP-L and also to competitively inhibit attachment of BCG to matrix fibronectin. In vivo studies show FAP to be a necessary protein for the stable attachment of BCG to the bladder wall. Moreover, stable binding of BCG via FAP was shown to be necessary for the expression of BCG-induced antitumor activity. Our results demonstrate a biological role for FAP in the mediation of BCG-induced antitumor activity.

  16. Challenges faced by professional nurses when implementing the Expanded Programme on Immunisation at rural clinics in Capricorn District, Limpopo

    Directory of Open Access Journals (Sweden)

    Tebogo M. Mothiba

    2016-03-01

    Full Text Available Background: Immunisation is the cornerstone of primary healthcare. Apart from the provision of safe water, immunisation remains the most cost-effective public health intervention currently available. Immunisation prevents infectious conditions that are debilitating, fatal and have the potential to cause huge public health burdens, both financially and socially, in South Africa.Aim: To determine the challenges faced by professional nurses when implementing the Expanded Programme on Immunisation (EPI at rural clinics in Capricorn District, Limpopo Province, South Africa.Setting: The study was conducted in selected primary healthcare clinics of Capricorn District, Limpopo Province.Methods: A qualitative explorative descriptive contextual research design was used to gather data related to the challenges faced by professional nurses when implementing EPI at rural clinics in Capricorn District.Results: The findings revealed that professional nurses had knowledge of the programme, but that they experienced several challenges during implementation of EPI that included staff shortages and problems related to maintenance of the vaccines’ potency.Conclusions: The Department of Health as well as the nursing administration should monitor policies and guidelines, and especially maintenance of a cold chain for vaccines, to ensure that they are practised throughout Limpopo Province. The problem of staff shortages also needs to be addressed so that the EPI can achieve its targeted objectives.Keywords: Professional nurse, knowledge, EPI-SA, immunisation

  17. Delayed fission

    Energy Technology Data Exchange (ETDEWEB)

    Hatsukawa, Yuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-07-01

    Delayed fission is a nuclear decay process that couples {beta} decay and fission. In the delayed fission process, a parent nucleus undergoes {beta} decay and thereby populates excited states in the daughter. If these states are of energies comparable to or greater than the fission barrier of the daughter, then fission may compete with other decay modes of the excited states in the daughter. In this paper, mechanism and some experiments of the delayed fission will be discussed. (author)

  18. The Efficacy of the BCG Vaccine against Newly Emerging Clinical Strains of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Marcela Henao-Tamayo

    Full Text Available To date, most new vaccines against Mycobacterium tuberculosis, including new recombinant versions of the current BCG vaccine, have usually been screened against the laboratory strains H37Rv or Erdman. In this study we took advantage of our recent work in characterizing an increasingly large panel of newly emerging clinical isolates [from the United States or from the Western Cape region of South Africa], to determine to what extent vaccines would protect against these [mostly high virulence] strains. We show here that both BCG Pasteur and recombinant BCG Aeras-422 [used here as a good example of the new generation BCG vaccines] protected well in both mouse and guinea pig low dose aerosol infection models against the majority of clinical isolates tested. However, Aeras-422 was not effective in a long term survival assay compared to BCG Pasteur. Protection was very strongly expressed against all of the Western Cape strains tested, reinforcing our viewpoint that any attempt at boosting BCG would be very difficult to achieve statistically. This observation is discussed in the context of the growing argument made by others that the failure of a recent vaccine trial disqualifies the further use of animal models to predict vaccine efficacy. This viewpoint is in our opinion completely erroneous, and that it is the fitness of prevalent strains in the trial site area that is the centrally important factor, an issue that is not being addressed by the field.

  19. Bacillus Calmette-Guérin immunisation at birth and morbidity among Danish children

    DEFF Research Database (Denmark)

    Thøstesen, Lisbeth Marianne; Nissen, Thomas Nørrelykke; Kjærgaard, Jesper;

    2015-01-01

    days of life, infants were randomly assigned to intra-dermal vaccination with BCG or no intervention. At 3 and 13 months of age structured telephone interviews and clinical examinations of the children were conducted. In a subgroup of children blood samples were drawn and stool samples collected at age......, wheezing, eczema, use of prescribed medication, growth, development, thymus index, T- and B-cell subpopulations assessed by flow cytometry, in vitro cytokine responses and specific antibody responses to other vaccines. Adverse reactions were registered. DISCUSSION: With participation of 4184 families...... and more than 93% adherence to clinical follow-up at 3 and 13 months, this randomised clinical trial has the potential to create evidence regarding non-specific effects of BCG vaccination in a high-income setting....

  20. Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000-2002

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik

    2005-01-01

    The rates of positive tuberculin skin test (TST) reactions and BCG scarring after BCG vaccination vary between studies and populations. Tuberculin reactivity and BCG scarring may be related to better child survival in low-income countries. We therefore studied determinants for TST reaction......=2225) of age. In a subgroup of the children the vaccination technique was monitored by direct observation of post-vaccination wheal and route of administration. Three different types of BCG vaccine supplied by the local Extended Programme on Immunization were used. At 6 months of age the rate of PPD.......66 (1.24-2.21)). In the multivariable analyses of BCG-vaccinated children assessed at 6 months of age, monitoring of vaccination technique and type of BCG vaccine were important. This was not changed by control for other determinants, including sex, season, vaccination place, birthplace, ethnic group...

  1. Immune response in hamsters immunised with a recombinant fragment of LigA from Leptospira interrogans, associated with carrier molecules

    Directory of Open Access Journals (Sweden)

    Thaís L Oliveira

    Full Text Available Immunisation with the C-terminal region of leptospiral immunoglobulin-like A protein (LigANI has shown promising results against leptospirosis. We evaluated the humoral immune response and protection induced by LigANI associated with carboxyl multi-walled carbon nanotubes (COOH-MWCNTs, CpG oligodeoxynucleotides (CpG ODNs, or Alhydrogel. Animals immunised with CpG ODNs were unable to develop a humoral immune response, whereas immunisation with LigANI and COOH-MWCNTs produced a high level of IgG antibodies, similar to that with LigANI and Alhydrogel, but it was not protective. The use of carbon nanotubes as an adjuvant in subunit vaccines against leptospirosis is a novel approach for improving specific IgG production.

  2. Immune response in hamsters immunised with a recombinant fragment of LigA from Leptospira interrogans, associated with carrier molecules

    Science.gov (United States)

    Oliveira, Thaís L; Bacelo, Kátia L; Schuch, Rodrigo A; Seixas, Fabiana K; Collares, Tiago; Rodrigues, Oscar ED; Vargas, Josimar; do Nascimento, Rafaella O; Dellagostin, Odir A; Hartwig, Daiane D

    2016-01-01

    Immunisation with the C-terminal region of leptospiral immunoglobulin-like A protein (LigANI) has shown promising results against leptospirosis. We evaluated the humoral immune response and protection induced by LigANI associated with carboxyl multi-walled carbon nanotubes (COOH-MWCNTs), CpG oligodeoxynucleotides (CpG ODNs), or Alhydrogel. Animals immunised with CpG ODNs were unable to develop a humoral immune response, whereas immunisation with LigANI and COOH-MWCNTs produced a high level of IgG antibodies, similar to that with LigANI and Alhydrogel, but it was not protective. The use of carbon nanotubes as an adjuvant in subunit vaccines against leptospirosis is a novel approach for improving specific IgG production. PMID:27759768

  3. Protection of European domestic pigs from virulent African isolates of African swine fever virus by experimental immunisation.

    Science.gov (United States)

    King, Katherine; Chapman, Dave; Argilaguet, Jordi M; Fishbourne, Emma; Hutet, Evelyne; Cariolet, Roland; Hutchings, Geoff; Oura, Christopher A L; Netherton, Christopher L; Moffat, Katy; Taylor, Geraldine; Le Potier, Marie-Frederique; Dixon, Linda K; Takamatsu, Haru-H

    2011-06-20

    African swine fever (ASF) is an acute haemorrhagic disease of domestic pigs for which there is currently no vaccine. We showed that experimental immunisation of pigs with the non-virulent OURT88/3 genotype I isolate from Portugal followed by the closely related virulent OURT88/1 genotype I isolate could confer protection against challenge with virulent isolates from Africa including the genotype I Benin 97/1 isolate and genotype X Uganda 1965 isolate. This immunisation strategy protected most pigs challenged with either Benin or Uganda from both disease and viraemia. Cross-protection was correlated with the ability of different ASFV isolates to stimulate immune lymphocytes from the OURT88/3 and OURT88/1 immunised pigs.

  4. Immunisation against PCV2 structural protein by DNA vaccination of mice

    DEFF Research Database (Denmark)

    Kamstrup, Søren; Barfoed, Annette Malene; Frimann, Tine;

    2004-01-01

    -protective levels around weaning at 3-5-weeks of age. If immunoprophylaxis is to be effective, an immunisation method capable of breaking through maternal immunity must be employed. In this study, we have developed and investigated the potential of a DNA vaccination approach to be one such method. The gene encoding...... the capsid protein of PCV2 was cloned in a DNA vaccination plasmid and expression of capsid protein was demonstrated in vitro. Mice were gene gun vaccinated three timesand all mice responded serologically by raising antibodies against PCV2. The results suggest, that DNA based vaccination might offer...... opportunities for vaccination of piglets against PCV2....

  5. Hepatitis B immunisation programmes in European Union, Norway and Iceland: where we were in 2009?

    Science.gov (United States)

    Mereckiene, Jolita; Cotter, Suzanne; Lopalco, Pierluigi; D'Ancona, Fortunato; Levy-Bruhl, Daniel; Giambi, Cristina; Johansen, Kari; Dematte, Luca; Salmaso, Stefania; Stefanoff, Pawel; O'Flanagan, Darina

    2010-06-17

    In January 2009 25 European Union (EU) Member States (MSs), Norway and Iceland, participated in a survey seeking information on national hepatitis B vaccination programmes. Details of vaccination policy, schedule, population groups targeted for vaccination, programme funding, vaccine coverage and methods of monitoring of vaccine coverage were obtained. Twenty (74%) countries reported that they have a universal hepatitis B vaccination programme, in addition to immunisation of at risk groups; seven (26%) countries recommend HBV for high risk groups only (with some inter-country variation on groups considered at high risk). Among countries without universal hepatitis B vaccination programmes, the major factor for non-introduction is low disease endemicity.

  6. [Increase in the production of oncovirus type C by an L929 cell culture as a result of BCG infection].

    Science.gov (United States)

    Klitsunova, N V; Gosteva, V V; Kim, A A; Bykovskiĭ, A F

    1984-01-01

    The effect of BCG infection of L929 cells on replication of oncovirus type C was studied. Ultrathin sections of the BCG-infected culture were examined electron microscopically 1, 3, 6, 8, and 10 days postinfection. Most microorganisms with the morphology typical of mycobacteria were found inside phagosomes. The number of extracellular virions as well as budding and abnormal forms per one cell contour was counted. BCG-infected cells were found to produce significantly more virus than the controls. The difference was maximal 3 days postinoculation. Possible reasons for the increased oncovirus production by continuous cell lines after infection with BCG are discussed.

  7. Economic rate of discount and estimating cost benefit of viral immunisation programmes.

    Science.gov (United States)

    West, R R

    1999-01-01

    Many individual and societal decisions over purchase (or investment) involve consideration of timing, in that either the price may be paid now and the benefit enjoyed some time in the future or the converse the benefit enjoyed now and the price paid later. Since most individuals generally prefer the present to the future, economic theory has conventionally discounted future costs or benefits to estimate 'net present values'. The rationale for this is principally based on future uncertainty. In recent years, economists have turned their attention to valuing health as an economic 'good'. Observations of individual behaviour would imply that individuals discount future health, as other potential benefits, mostly because there is some uncertainty about their futures. Although economic theory is strongly predicated on the 'sovereignty of the individual', it does not necessarily follow that society discounts the future as do individuals, since for society the future is not so uncertain. Society's endorsement of many public health and preventive medicine objectives, which seek health gains in the future (rather than the present), imply that society's rate of discount may be appreciably lower than that of individuals. In immunisation, arguably one of the most effective of preventive measures, there is the additional benefit to others attributable to herd immunity. This paper argues that the future health gains for society arising from immunisation should not be underestimated by application of inappropriate discounting.

  8. Impact of a measles immunisation campaign on measles admissions to a Natal hospital.

    Science.gov (United States)

    Abdool Karim, S S; Abdool Karim, Q; Chamane, M

    1991-12-07

    During May and June 1990, a national mass measles immunisation campaign was undertaken in South Africa. This study is an assessment of the impact of the campaign on measles admissions to a provincial referral hospital that has specifically designated wards for children with communicable diseases. Data from the measles ward admissions book for the 18 months before the campaign (1 January 1989-30 June 1990) and 6 months after the campaign (1 July 1990-31 December 1990) were compared. Since the campaign, the average number of measles admissions has declined by 64.4% from 87 to 31 per month (P less than 0.01). Before the campaign, 21.3% of measles patients admitted were aged 7-9 months compared with 27.6% after the campaign, highlighting the urgent need to improve the measles vaccination coverage in this age group. An analysis of the geographical source of patients showed that measles continued to occur after the campaign in most of the areas where it existed before the campaign. It is concluded that important gains have been achieved by the campaign. These will be rapidly eroded and epidemics of measles may occur if measles vaccination efforts wane and slump back to pre-campaign levels. It is important to capitalise on the momentum generated through the campaign by continuing to support efforts of existing health care services to improve and maintain high levels of measles immunisation coverage.

  9. Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation

    Science.gov (United States)

    Caetano, Liliana A.; Almeida, António J.; Gonçalves, Lídia M.D.

    2016-01-01

    The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. PMID:27187418

  10. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, A.E.; Benn, Christine Stabell; Ravn, H.;

    2010-01-01

    controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated...... children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrolment (hazard...... ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrolment (1.78, 1.04 to 3.04). Conclusions There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions...

  11. [Immune reconstitution syndrome due to BCG in HIV-treated children].

    Science.gov (United States)

    Miranda-Choque, Edwin; Candela-Herrera, Jorge; R Segura, Eddy; Farfán-Ramos, Sonia; Barriga, Aldo

    2012-01-01

    The objective of this study is to describe the clinical profile of the immune reconstitution syndrome due to Mycobacterium bovis Bacillus Calmette-Guérin (IRS-BCG) in children with HIV infection who receive highly active antiretroviral treatment (HAART) at Instituto Nacional de Salud del Niño de Lima (National Children's Health Institute of Lima), Peru. A case study was conducted, including 8 children with IRS-BCG, defined as the presence of regional lymphadenopathy or inflammation on the BCG vaccination site with at least one less logarithm in the viral load or immune improvement. All patients had AIDS (C3). The starting median age in HAART was 7.2 months and the event occurred 3 to 11 weeks after the treatment was started. 7 cases showed axillary adenitis. When compared with the Non IRS-BCG group, a significant association between the age at which HAART was started at one year, severe immunodepression, and increased viral load was found. It is concluded that IRS-BCG was related to a rapid clinical progression of the mother-to-child transmitted HIV/AIDS infection, severe immunosuppression and high viral load when the HAART began.

  12. Adverse Events Following Immunisation under the National Vaccination Programme of The Netherlands Number XI - Reports in 2004

    NARCIS (Netherlands)

    Vermeer-de Bondt PE; Dzaferagic A; Phaff TAJ; Wesselo C; Maas NAT van der; CIE

    2006-01-01

    Adverse events following immunisation (AEFI) in the National Vaccination Programme of the Netherlands (RVP) have been monitored through an enhanced passive surveillance system by RIVM since 1962. From 1984 until 2003 evaluation has been done in close collaboration with the Health Council. An RIVM ex

  13. Immunisation of rhesus monkeys with Streptococcus mutans, Lactobacillus acidophilus and lipoteichoic acid for protection against dental caries.

    Science.gov (United States)

    Caldwell, J; Lehner, T

    1982-08-01

    An attempt was made to protect rhesus monkeys from dental caries by immunisation with Streptococcus mutans, Lactobacillus acidophilus and lipoteichoic acid (LTA). The vaccine composed of S. mutans gave significant protection against caries, a decrease in the number of S. mutans, an increase in IgG antibodies and a moderate increase in complement-fixing antibodies to LTA. When LTA was used as immunogen, there was only a small reduction in caries, without any detectable antibodies to LTA and a slight increase in IgG antibodies to cell of S. mutans. Vaccines of L. acidophilus or L. fermentum gave no protection. A combined vaccine of S. mutans and L. acidophilus did not reduce the incidence of caries but the antibody titre to cells of S. mutans was raised to a level comparable with that in the S. mutans-immunised monkeys. The results of this investigation in a subhuman primate confirm that immunisation with S. mutans induces protection against caries, unlike the attempt to immunise with two selected strains of lactobacilli. More studies are required to establish the role of specific serotypes of lactobacilli in the development of dental caries.

  14. Correlation of haemagglutinin-neuraminidase and fusion protein content with protective antibody response after immunisation with inactivated Newcastle disease vaccines.

    NARCIS (Netherlands)

    Maas, R.A.; Komen, M.; Diepen, van M.; Oei, H.L.; Claassen, I.J.T.M.

    2003-01-01

    The correlation between the antigen content of inactivated Newcastle disease (ND) oil emulsion-vaccines and the serological response after immunisation was studied. The haemagglutinin-neuraminidase (HN) and fusion (F) proteins of Newcastle disease virus (NDV) were quantified in 33 inactivated oil-ad

  15. Tolerance and immune response to the porcine endogenous retrovirus in German landrace pigs immunised with viral proteins.

    Science.gov (United States)

    Denner, Joachim; Petersen, Björn; Niemann, Heiner

    2015-10-02

    Immunisation of goats, mice, rats, rabbits, guinea pigs, and hamsters with the recombinant ectodomain of the porcine endogenous retrovirus (PERV) transmembrane envelope (TM) protein (p15E) induced binding and neutralising immune antibodies in all animals. In contrast, no antibodies were induced when pigs were immunised with p15E, indicating that pigs are tolerant to their endogenous retroviruses, at least to the TM protein. To answer the question of whether pigs are tolerant to other structural proteins of PERV, we immunised German landrace pigs with p15E, this time in conjunction with the surface envelope proteins gp70 and the core capsid Gag protein p27CA. To ensure that the pigs were immunocompetent and that immunisation was successful, all animals also received an injection of an unrelated protein, keyhole limpet hemocyanin (KLH). Whereas all animals produced antibodies against KLH, no animals produced antibodies against the viral envelope proteins, thus confirming previous results for p15E and extending them to the other envelope protein, gp70. However, the pigs did produce antibodies against p27CA, indicating that there is no tolerance to the core capsid protein of PERV.

  16. Immunogenicity of recombinant HBsAg/HCV particles in mice pre-immunised with hepatitis B virus-specific vaccine.

    Science.gov (United States)

    Netter, Hans J; Woo, Wai-Ping; Tindle, Robert; Macfarlan, Roderick I; Gowans, Eric J

    2003-06-20

    Due to their spatial structure virus-like particles (VLPs) generally induce effective immune responses. VLPs derived from the small envelope protein (HBsAg-S) of hepatitis B virus (HBV) comprise the HBV vaccine. Modified HBsAs-S VLPs, carrying the immunodominant hypervariable region (HVR1) of the hepatitis C virus (HCV) envelope protein E2 within the exposed 'a'-determinant region (HBsAg/HVR1-VLPs), elicited HVR1-specific antibodies in mice. A high percentage of the human population is positive for anti-HBsAg antibodies (anti-HBs), either through vaccination or natural infection. We, therefore, determined if pre-existing anti-HBs could influence immunisation with modified VLPs. Mice were immunised with a commercial HBV vaccine, monitored to ensure an anti-HBs response, then immunised with HBsAg/HVR1-VLPs. The resulting anti-HVR1 antibody titre was similar in mice with or without pre-existing anti-HBs. This suggests that HBsAg/HVR1-VLPs induce a primary immune response to HVR1 in anti-HBs positive mice and, hence, they may be used successfully in individuals already immunised with the HBV vaccine.

  17. UNderstanding uptake of Immunisations in TravellIng aNd Gypsy communities (UNITING): a qualitative interview study.

    Science.gov (United States)

    Jackson, Cath; Dyson, Lisa; Bedford, Helen; Cheater, Francine M; Condon, Louise; Crocker, Annie; Emslie, Carol; Ireland, Lana; Kemsley, Philippa; Kerr, Susan; Lewis, Helen J; Mytton, Julie; Overend, Karen; Redsell, Sarah; Richardson, Zoe; Shepherd, Christine; Smith, Lesley

    2016-01-01

    BACKGROUND Gypsies, Travellers and Roma (referred to as Travellers) are less likely to access health services, including immunisation. To improve immunisation rates, we need to understand what helps and hinders individuals in these communities in taking up immunisations. AIMS (1) Investigate the barriers to and facilitators of acceptability and uptake of immunisations among six Traveller communities across four UK cities; and (2) identify possible interventions to increase uptake of immunisations in these Traveller communities that could be tested in a subsequent feasibility study. METHODS Three-phase qualitative study underpinned by the social ecological model. Phase 1: interviews with 174 Travellers from six communities: Romanian Roma (Bristol); English Gypsy/Irish Traveller (Bristol); English Gypsy (York); Romanian/Slovakian Roma (Glasgow); Scottish Showpeople (Glasgow); and Irish Traveller (London). Focus on childhood and adult vaccines. Phase 2: interviews with 39 service providers. Data were analysed using the framework approach. Interventions were identified using a modified intervention mapping approach. Phase 3: 51 Travellers and 25 service providers attended workshops and produced a prioritised list of potentially acceptable and feasible interventions. RESULTS There were many common accounts of barriers and facilitators across communities, particularly across the English-speaking communities. Scottish Showpeople were the most similar to the general population. Roma communities experienced additional barriers of language and being in a new country. Men, women and service providers described similar barriers and facilitators. There was widespread acceptance of childhood and adult immunisation, with current parents perceived as more positive than their elders. A minority of English-speaking Travellers worried about multiple/combined childhood vaccines, adult flu and whooping cough. Cultural concerns about vaccines offered during pregnancy and about human

  18. A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence.

    Science.gov (United States)

    Shoen, Carolyn M; DeStefano, Michelle S; Hager, Cynthia C; Tham, Kyi-Toe; Braunstein, Miriam; Allen, Alexandria D; Gates, Hiriam O; Cynamon, Michael H; Kernodle, Douglas S

    2013-01-11

    Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  19. A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

    Directory of Open Access Journals (Sweden)

    Douglas S. Kernodle

    2013-01-01

    Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  20. Mechanism responsible for the antitumor effect of BCG-CWS using the LEEL method in a mouse bladder cancer model.

    Science.gov (United States)

    Nakamura, Takashi; Fukiage, Masafumi; Suzuki, Yoshiteru; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Harashima, Hideyoshi

    2014-12-28

    We previously reported on the development of a water soluble formulation of the cell wall skeleton of BCG (BCG-CWS), a major immune active center of BCG, by encapsulating it into a nanoparticle (CWS-NP). The CWS-NP allowed us to clarify the machinery associated with the BCG mediated anti-bladder tumor effect, especially the roles of bladder cancer cells and dendritic cells (DCs) in the initial step, which remains poorly understood. We show herein that the internalization of BCG-CWS by bladder cancer cells, but not DCs, is indispensable for the induction of an antitumor effect against bladder cancer. Tumor growth was significantly inhibited in mice that had been inoculated with mouse bladder cancer (MBT-2) cells containing internalized BCG-CWS. On the other hand, the internalization of BCG-CWS by DCs had only a minor effect on inducing an antitumor effect against MBT-2 tumors. This was clarified for the first time by using the CWS-NP. This finding provides insights into our understanding of the role of bladder cancer cells and DCs in BCG therapy against bladder cancer.

  1. Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Larsen, Nanna; Biering-Sørensen, Sofie

    2015-01-01

    BACKGROUND:  Bacillus Calmette-Guérin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia. METHODS:  Within a randomized trial in LBW infants in Guin...

  2. Integrated package approach in delivering interventions during immunisation campaigns in a complex environment in Papua New Guinea: a case study.

    Science.gov (United States)

    Vince, John David; Datta, Siddhartha Sankar; Toikilik, Steven; Lagani, William

    2014-08-06

    Papua New Guinea's difficult and varied topography, poor transport infrastructure, changing dynamics of population and economy in recent times and understaffed and poorly financed health service present major challenges for successful delivery of vaccination and other preventative health interventions to both the rural majority and urban populations, thereby posing risks for vaccine preventable disease outbreaks in the country. The country has struggled to meet the vaccination coverage targets required for the eradication of poliomyelitis and elimination of measles. Escalation of inter and intra country migration resulting from major industrial developments, particularly in extraction industries, has substantially increased the risk of infectious disease importation. This case study documents the evolution of immunisation programmes since the introduction of supplementary immunisation activities (SIAs). Single antigen SIAs have advantages and disadvantages. In situations in which the delivery of preventative health interventions is difficult, it is likely that the cost benefit is greater for multiple than for single intervention. The lessons learned from the conduct of single antigen SIAs can be effectively used for programmes delivering multiple SIA antigens, routine immunisations, and other health interventions. This paper describes a successful and cost effective multiple intervention programme in Papua New Guinea. The review of the last SIA in Papua New Guinea showed relatively high coverage of all the interventions and demonstrated the operational feasibility of delivering multiple interventions in resource constrained settings. Studies in other developing countries such as Lesotho and Ethiopia have also successfully integrated health interventions with SIA. In settings such as Papua New Guinea there is a strong case for integrating supplementary immunisation activity with routine immunisation and other health interventions through a comprehensive outreach

  3. Optimal control on bladder cancer growth model with BCG immunotherapy and chemotherapy

    Science.gov (United States)

    Dewi, C.; Trisilowati

    2015-03-01

    In this paper, an optimal control model of the growth of bladder cancer with BCG (Basil Calmate Guerin) immunotherapy and chemotherapy is discussed. The purpose of this optimal control is to determine the number of BCG vaccine and drug should be given during treatment such that the growth of bladder cancer cells can be suppressed. Optimal control is obtained by applying Pontryagin principle. Furthermore, the optimal control problem is solved numerically using Forward-Backward Sweep method. Numerical simulations show the effectiveness of the vaccine and drug in controlling the growth of cancer cells. Hence, it can reduce the number of cancer cells that is not infected with BCG as well as minimize the cost of the treatment.

  4. A Trend Analysis of Competition Positioning in Chinese Seaports by Using DEA Model and BCG Matrix

    Institute of Scientific and Technical Information of China (English)

    Hoki Nam

    2007-01-01

    <正>This paper has shown the trend of competition positioning of ten critical Chinese seaports from 2003 to 2006 by using DEA model for the performance efficiency analysis and BCG matrix,which consists of relative market share and growth rate as well as the scores of both BCC and CCR in the vertical and horizontal axis of BCG matrix.The expected results will include the total economic efficiency ranking of each Chinese seaport,and the relative competitive positioning in terms of growth rate and efficiency scores.The main policy implication of this paper is to emphasize the DEA model and BCG matrix method can support the seaport managers the basic information for planning the future port management for enhancing the competitive positioning among Chinese seaports.

  5. SAPHO syndrome with bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer.

    Science.gov (United States)

    Matsumaru, Katsuhiko; Nagai, Kazuki; Murakami, Takayuki; Andoh, Kazuo

    2010-08-31

    The authors describe a case of SAPHO syndrome with bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer. The patient had undergone transurethral resection (TUR) and was treated with BCG immunotherapy following TUR. Two years after treatment for bladder cancer, the patient had palmoplantar pustulosis, and in the past 1 month suffered from pain localised to the anterior chest wall. The bone scintigraphy showed a strong focal enrichment in the right chest wall, suggesting spondyloarthropathy rather than malignant disease. On the basis of clinical and scintigraphy findings, SAPHO syndrome was diagnosed. The patient was treated with topical therapy and non-steroidal anti-inflammatory drugs and symptoms improved. The authors suggest that SAPHO syndrome might be caused by an association with BCG immunotherapy.

  6. Stable Expression of Lentiviral Antigens by Quality-Controlled Recombinant Mycobacterium bovis BCG Vectors.

    Science.gov (United States)

    Hart, Bryan E; Asrican, Rose; Lim, So-Yon; Sixsmith, Jaimie D; Lukose, Regy; Souther, Sommer J R; Rayasam, Swati D G; Saelens, Joseph W; Chen, Ching-Ju; Seay, Sarah A; Berney-Meyer, Linda; Magtanong, Leslie; Vermeul, Kim; Pajanirassa, Priyadharshini; Jimenez, Amanda E; Ng, Tony W; Tobin, David M; Porcelli, Steven A; Larsen, Michelle H; Schmitz, Joern E; Haynes, Barton F; Jacobs, William R; Lee, Sunhee; Frothingham, Richard

    2015-07-01

    The well-established safety profile of the tuberculosis vaccine strain, Mycobacterium bovis bacille Calmette-Guérin (BCG), makes it an attractive vehicle for heterologous expression of antigens from clinically relevant pathogens. However, successful generation of recombinant BCG strains possessing consistent insert expression has encountered challenges in stability. Here, we describe a method for the development of large recombinant BCG accession lots which stably express the lentiviral antigens, human immunodeficiency virus (HIV) gp120 and simian immunodeficiency virus (SIV) Gag, using selectable leucine auxotrophic complementation. Successful establishment of vaccine stability stems from stringent quality control criteria which not only screen for highly stable complemented BCG ΔleuCD transformants but also thoroughly characterize postproduction quality. These parameters include consistent production of correctly sized antigen, retention of sequence-pure plasmid DNA, freeze-thaw recovery, enumeration of CFU, and assessment of cellular aggregates. Importantly, these quality assurance procedures were indicative of overall vaccine stability, were predictive for successful antigen expression in subsequent passaging both in vitro and in vivo, and correlated with induction of immune responses in murine models. This study has yielded a quality-controlled BCG ΔleuCD vaccine expressing HIV gp120 that retained stable full-length expression after 10(24)-fold amplification in vitro and following 60 days of growth in mice. A second vaccine lot expressed full-length SIV Gag for >10(68)-fold amplification in vitro and induced potent antigen-specific T cell populations in vaccinated mice. Production of large, well-defined recombinant BCG ΔleuCD lots can allow confidence that vaccine materials for immunogenicity and protection studies are not negatively affected by instability or differences between freshly grown production batches.

  7. Intratumoral injection of BCG-CWS-pretreated dendritic cells following tumor cryoablation.

    Science.gov (United States)

    Kawamura, Naoshi; Udagawa, Masaru; Fujita, Tomonobu; Sakurai, Toshiharu; Yaguchi, Tomonori; Kawakami, Yutaka

    2014-01-01

    Intratumoral administration of dendritic cells (DC) following cryoablation of tumor is one of the personalized cancer immunotherapies which is able to induce immune responses to multiple endogenous tumor antigens, including shared and unique antigens. Here we describe protocols of cryoablation of tumors, generation of cultured DC, pretreatment of DC with a Toll-like receptor (TLR)-stimulating purified component of Bacillus Calmette-Guerin cell wall fraction (BCG-CWS) and highly immunogenic keyhole limpet hemocyanin (KLH) antigen, and combined use of tumor cryoablation and intratumoral administration of BCG-CWS-pretreated DC in both a murine model and cancer patients.

  8. A Complication of BCG Vaccine: A Case of Localized Cutaneous Abscess due to Mycobacterium bovis

    Directory of Open Access Journals (Sweden)

    Nathalie Lussier

    1999-01-01

    Full Text Available The attenuated bacille Calmette-Guérin (BCG vaccine is administered to prevent tuberculosis. Complications of vaccination are uncommon. A case of cutaneous abscess due to BCG is presented in a 24-year-old woman. The abscess developed at the inoculation site four weeks after vaccination. Routine Gram stain and bacterial cultures of the pus were negative. The auramine stain was positive. Mycobacterial cultures were positive after 14 and 18 days, using the BACTEC 12B bottle and Löwenstein-Jensen media, respectively. The mycobacteria were identified as Mycobacterium bovis, vaccinal strain by high-performance liquid chromatography and DNA probe assays.

  9. Diphtheria-like illness in a fully immunised child caused by Corynebacterium pseudodiphtheriticum

    Directory of Open Access Journals (Sweden)

    V A Indumathi

    2014-01-01

    Full Text Available Corynebacterium pseudodiphtheriticum is a common commensal flora of the upper respiratory tract in humans. Though the pathogenicity of C. pseudodiphtheriticum is not rare, its role as an opportunistic pathogen is mainly limited to the lower respiratory tract, particularly in patients with underlying systemic conditions or immune-compromisation. We hereby present the first case of C. pseudodiphtheriticum causing diphtheria-like illness affecting the upper respiratory tract of a 6-year-old fully immunised otherwise healthy child. In countries with very low incidence of diphtheria, C. pseudodiphtheriticum should be included in differential diagnosis for a child presenting with diphtheria-like illness. Simple, rapid screening tests should be used to differentiate it from C. diphtheriae and hence, to prevent unnecessary concern in community.

  10. Fault diagnosis based on support vector machines with parameter optimisation by artificial immunisation algorithm

    Science.gov (United States)

    Yuan, Shengfa; Chu, Fulei

    2007-04-01

    Support vector machines (SVM) is a new general machine-learning tool based on the structural risk minimisation principle that exhibits good generalisation when fault samples are few, it is especially fit for classification, forecasting and estimation in small-sample cases such as fault diagnosis, but some parameters in SVM are selected by man's experience, this has hampered its efficiency in practical application. Artificial immunisation algorithm (AIA) is used to optimise the parameters in SVM in this paper. The AIA is a new optimisation method based on the biologic immune principle of human being and other living beings. It can effectively avoid the premature convergence and guarantees the variety of solution. With the parameters optimised by AIA, the total capability of the SVM classifier is improved. The fault diagnosis of turbo pump rotor shows that the SVM optimised by AIA can give higher recognition accuracy than the normal SVM.

  11. The Cyclic Di-GMP Phosphodiesterase Gene Rv1357c/BCG1419c Affects BCG Pellicle Production and In Vivo Maintenance.

    Science.gov (United States)

    Flores-Valdez, Mario Alberto; Aceves-Sánchez, Michel de Jesús; Pedroza-Roldán, César; Vega-Domínguez, Perla Jazmín; Prado-Montes de Oca, Ernesto; Bravo-Madrigal, Jorge; Laval, Françoise; Daffé, Mamadou; Koestler, Ben; Waters, Christopher M

    2015-02-01

    Bacteria living in a surface-attached community that contains a heterogeneous population, coated with an extracellular matrix, and showing drug tolerance (biofilms) are often linked to chronic infections. In mycobacteria, the pellicle mode of growth has been equated to an in vitro biofilm and meets several of the criteria mentioned above, while tuberculosis infection presents a chronic (latent) phase of infection. As mycobacteria lack most genes required to control biofilm production by other microorganisms, we deleted or expressed from the hsp60 strong promoter the only known c-di-GMP phosphodiesterase (PDE) gene in Mycobacterium bovis BCG. We found changes in pellicle production, cellular protein profiles, lipid production, resistance to nitrosative stress and maintenance in lungs and spleens of immunocompetent BALB/mice. Our results show that pellicle production and capacity to remain within the host are linked in BCG.

  12. Re: Sequential Combination of Mitomycin C Plus Bacillus Calmette-Guerin (BCG Is More Effective but More Toxic Than BCG Alone in Patients with Non–Muscle-Invasive Bladder Cancer in Intermediate-and High-Risk Patients: Final Outcome of CUETO 93009, A Randomized Prospective Trial

    Directory of Open Access Journals (Sweden)

    Eduardo Solsona

    2015-03-01

    Full Text Available EAU Guideline recommendation in non-muscle invasive bladder cancer (NMIBC is that patients who have intermediate or high risk for recurrence and intermediate risk for progression should receive early single dose intravesical chemotherapy followed by maintenance or a minimum of 1 year of BCG. Intravesical Mitomycin C (MMC plus Bacillus Calmette-Guerin (BCG treatment schemes were studied. However, MMC+BCG were not found to be superior to BCG alone (1,2. In the present study, authors conducted a randomized prospective trial on combination of MMC+BCG (n=192 or BCG alone (n=190. EORTC definition of NMIBC intermediate and high-risk patientswere included in the study. Unlike previous reported studies, disease-free interval at 5 years for MMC+BCG was found to be significantly better (HR: 0.57; 95% CI, 0.39 -0,83; p=0.003 than BCG alone. In an interim analysis, excessive toxicity was observed in MMC+BCG than BCG alone group. Consequently MMC dose was reduced from 30 mg to 10 mg. However, toxicity remained higher in the MMC+BCG group. Especially in EORTC highrisk NMIBCs, MMC+BCG is better than BCG alone, but with worse toxicity. In conclusion, despite some limitations, the results of Solsona et al. provided a new potential bladder-sparing management alternative, but it has higher toxicity. Additional studies are required to confirm these findings and availability of a less toxic intravesical chemotherapeutic agent.

  13. Toxicogenomic response of Mycobacterium bovis BCG to peracetic acid and a comparative analysis of the M. bovis BCG response to three oxidative disinfectants.

    Science.gov (United States)

    Nde, Chantal W; Toghrol, Freshteh; Jang, Hyeung-Jin; Bentley, William E

    2011-04-01

    Tuberculosis is a leading cause of death worldwide and infects thousands of Americans annually. Mycobacterium bovis causes tuberculosis in humans and several animal species. Peracetic acid is an approved tuberculocide in hospital and domestic environments. This study presents for the first time the transcriptomic changes in M. bovis BCG after treatment with 0.1 mM peracetic acid for 10 and 20 min. This study also presents for the first time a comparison among the transcriptomic responses of M. bovis BCG to three oxidative disinfectants: peracetic acid, sodium hypochlorite, and hydrogen peroxide after 10 min of treatment. Results indicate that arginine biosynthesis, virulence, and oxidative stress response genes were upregulated after both peracetic acid treatment times. Three DNA repair genes were downregulated after 10 and 20 min and cell wall component genes were upregulated after 20 min. The devR-devS signal transduction system was upregulated after 10 min, suggesting a role in the protection against peracetic acid treatment. Results also suggest that peracetic acid and sodium hypochlorite both induce the expression of the ctpF gene which is upregulated in hypoxic environments. Further, this study reveals that in M. bovis BCG, hydrogen peroxide and peracetic acid both induce the expression of katG involved in oxidative stress response and the mbtD and mbtI genes involved in iron regulation/virulence.

  14. Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

    2016-05-13

    Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

  15. Auxotrophic complementation as a selectable marker for stable expression of foreign antigens in Mycobacterium bovis BCG.

    Science.gov (United States)

    Borsuk, Sibele; Mendum, Tom A; Fagundes, Michel Quevedo; Michelon, Marcelo; Cunha, Cristina Wetzel; McFadden, Johnjoe; Dellagostin, Odir Antônio

    2007-11-01

    Mycobacterium bovis BCG has the potential to be an effective live vector for multivalent vaccines. However, most mycobacterial cloning vectors rely on antibiotic resistance genes as selectable markers, which would be undesirable in any practical vaccine. Here we report the use of auxotrophic complementation as a selectable marker that would be suitable for use in a recombinant vaccine. A BCG auxotrophic for the amino acid leucine was constructed by knocking out the leuD gene by unmarked homologous recombination. Expression of leuD on a plasmid not only allowed complementation, but also acted as a selectable marker. Removal of the kanamycin resistance gene, which remained necessary for plasmid manipulations in Escherichia coli, was accomplished by two different methods: restriction enzyme digestion followed by re-ligation before BCG transformation, or by Cre-loxP in vitro recombination mediated by the bacteriophage P1 Cre Recombinase. Stability of the plasmid was evaluated during in vitro and in vivo growth of the recombinant BCG in comparison to selection by antibiotic resistance. The new system was highly stable even during in vivo growth, as the selective pressure is maintained, whereas the conventional vector was unstable in the absence of selective pressure. This new system will now allow the construction of potential recombinante vaccine strains using stable multicopy plasmid vectors without the inclusion of antibiotic resistance markers.

  16. Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment

    DEFF Research Database (Denmark)

    Sartono, Erliyani; Lisse, Ida M; Terveer, Elisabeth M;

    2010-01-01

    BACKGROUND: Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did...

  17. BCG vaccine-induced neuroprotection in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Yong, Jing; Lacan, Goran; Dang, Hoa; Hsieh, Terry; Middleton, Blake; Wasserfall, Clive; Tian, Jide; Melega, William P; Kaufman, Daniel L

    2011-01-31

    There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions.

  18. Molecular networks discriminating mouse bladder responses to intravesical bacillus Calmette-Guerin (BCG, LPS, and TNF-α

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2008-02-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression in the bladder target organ beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following chronic intravesical BCG therapy and to compare the results to non-specific pro inflammatory stimuli (LPS and TNF-α. For this purpose, C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Seven days after the last instillation, the urothelium along with the submucosa was removed from detrusor muscle and the RNA was extracted from both layers for cDNA array experiments. Microarray results were normalized by a robust regression analysis and only genes with an expression above a conditional threshold of 0.001 (3SD above background were selected for analysis. Next, genes presenting a 3-fold ratio in regard to the control group were entered in Ingenuity Pathway Analysis (IPA for a comparative analysis in order to determine genes specifically regulated by BCG, TNF-α, and LPS. In addition, the transcriptome was precipitated with an antibody against RNA polymerase II and real-time polymerase chain reaction assay (Q-PCR was used to confirm some of the BCG-specific transcripts. Results Molecular networks of treatment-specific genes generated several hypotheses regarding the mode of action of BCG. BCG-specific genes involved small GTPases and BCG-specific networks overlapped with the following canonical signaling pathways: axonal guidance, B cell receptor, aryl hydrocarbon receptor, IL-6, PPAR, Wnt/β-catenin, and cAMP. In addition, a specific detrusor network expressed a high degree of overlap with the

  19. Construction, Expression and Identification of a Recombinant BCG Vaccine Encoding Human Mycobacterium Tuberculosis Heat Shock Protein 65

    Institute of Scientific and Technical Information of China (English)

    戴五星; 梁靓; 高红; 黄海浪; 陈智浩; 程继忠; 皇甫永穆

    2004-01-01

    Heat shock protein 65 (HSP65) is one of the most important protective immunogens against the tuberculosis infection. The signal sequence of antigen 85B and the whole HSP65 DNA sequence of human Mycobacterium tuberculosis (M. tuberculosis) were amplified from BCG genome and plasmid pCMV-MTHSP65 respectively by polymerase chain reactions (PCR). These two sequences were cloned into the plasmid pBCG-2100 under the control of the promoter of heat shock protein 70 (HSP70) from human M. tuberculosis, yielding the prokaryotic shuttle expression plasmid pBCG-SP-HSP65. Results of restriction endonuclease analysis, PCR detection and DNA sequencing analysis showed that the two cloned DNA sequences were consistent with those previously reported, and the direction of their inserting into the recombinant was correct and the reading frame had been maintained. The recombinants were electroporated into BCG to construct the recombinant BCG vaccine and induced by heating. The induced expression detected by SDS-PAGE showed that the content of 65 kD protein expressed in recombinant BCG was 35.69 % in total bacterial protein and 74.09 % in the cell lysate supernatants, suggesting that the recombinant HSP65 gene could express in BCG with high efficiency and the expressed proteins were mainly soluble. Western-blot showed that the secretive recombinant proteins could specifically combine with antibody against M.tuberculosis HSP65, indicating that the recombinant proteins possess the biological activity of HSP65.

  20. Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

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    Daniel H. Libraty

    2014-01-01

    Full Text Available Neonatal Bacille Calmette Guérin (BCG vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1 immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ producing spot-forming cells (SFC to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.

  1. 斑马鱼模型评价BCG-CpG-DNA的安全性%Evaluation of safety of BCG-CpG-DNA by using zebrafish model

    Institute of Scientific and Technical Information of China (English)

    王勇; 赵爱华; 陈将飞; 陈保文; 陈元红; 王国治

    2012-01-01

    目的 用斑马鱼模型对BCG-CpG-DNA进行安全性评价.方法 以斑马鱼胚胎为实验材料,将BCG-CpG-DNA设置4个浓度组(0.15、1.5、15、75 mg/L),暴露斑马鱼,以胚胎培养液暴露为空白对照组,以三甲基氯化锡(TMT)和全氟辛烷磺酸盐(PFOS)暴露为阳性对照组,胚胎期6 hpf(受精后6h)脱膜,8 hpf进行暴露毒性实验,研究其对斑马鱼发育、遗传、免疫以及行为的毒性影响.每组做3个重复,试验重复3次.结果 未观察到BCG-CpG-DNA各浓度组的斑马鱼胚胎明显的畸形和孵化死亡情况,其自主运动、触摸运动、行为检测、免疫强度检测与空白对照组相比,差异均无统计学意义(P>0.05).TMT对照组暴露对斑马鱼生长、发育、免疫及其神经等均有不同程度的影响,导致心胞肿大,对光暗刺激反应敏感,相对荧光强度明显增强,嗜中性粒细胞数量增多,对炎症的敏感性增强,与空白对照组相比,差异有统计学意义(P<0.05).结论 BCG-CpG-DNA暴露对斑马鱼生长、发育、免疫及其神经均无明显的急性毒性作用,在斑马鱼的胚胎暴露中具有较好的安全性.%Objective To evaluate the safety of BCG-CpG-DNA by using zebrafish model. Methods The embryos of ze-brafish were exposed to BCG-CpG-DNA at concentrations of 0. 15, 1. 5, 15 and 75 mg/L respectively, using those exposed to cul-ture liquid as blank control, and those exposed to TMT and PFOS as positive controls. Membrane shedding test was performed 6 h, while exposure toxicity test 8 h post fertilization to investigate the toxic effect on development, genetics, immune status and behavior of zebrafish. Each test was performed for 3 times in triplicate. Results No obvious monstrosities or deaths during incubation were ob-served in various test groups, while the autonomous movement, touch movement, behavior and immune level showed no significant difference with those in blank control group (P > 0. 05). However, TMT exposure showed

  2. A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection.

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    Yuan, Xuefeng; Teng, Xindong; Jing, Yukai; Ma, Jilei; Tian, Maopeng; Yu, Qi; Zhou, Lei; Wang, Ruibo; Wang, Weihua; Li, Li; Fan, Xionglin

    2015-12-01

    Tuberculosis (TB) remains one of the most menacing infectious diseases, although attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine has been widely used to protect children against primary TB. There are increasing evidences that rapid growing and dormant Mycobacterium tuberculosis (M. tuberculosis) coexist in vivo after infection. However, BCG vaccine only elicits cell-mediated immune responses to secretory antigens expressed by rapid growing pathogen. BCG vaccine is thus unable to thwart the reactivation of latent tuberculosis infection (LTBI), and its protection wanes over age after neonatal immunization. In order to extend its ability for a durable protection, a novel recombinant BCG (rBCG) strain, named rBCG::XB, was constructed by overexpressing immunodominant multistage antigens of Ag85B and HspX, which are expressed by both rapid replicating and dormant M. tuberculosis. Long-term protective effect and immunogenicity of rBCG::XB were compared with the parental BCG in vaccinated C57BL/6 mice. Our results demonstrated that rBCG::XB provided the stronger and long-lasting protection against M. tuberculosis H37Rv intranasal infection than BCG. The rBCG::XB not only elicited the more durable multistage antigen-specific CD4(+)Th1-biased immune responses and specific polyfunctional CD4(+)T cells but also augmented the CD8(+) CTL effects against Ag85B in vivo. In particular, higher levels of CD4(+) TEM and CD8(+) TCM cells, dominated by IL2(+) CD4(+) and CD8(+) TCM cells, were obtained in the spleen of rBCG::XB vaccinated mice. Therefore, our findings indicate that rBCG::XB is a promising candidate to improve the efficacy of BCG.

  3. Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells.

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    Taweewun Hunsawong

    2015-09-01

    Full Text Available Dengue viruses (DENVs are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world's population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV composed of UV-inactivated DENV-2 (UVI-DENV and Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (BCG-CWCs loaded into chitosan nanoparticles (CS-NPs. CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines.

  4. Glutamate Dehydrogenase Is Required by Mycobacterium bovis BCG for Resistance to Cellular Stress.

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    James L Gallant

    Full Text Available We recently reported on our success to generate deletion mutants of the genes encoding glutamate dehydrogenase (GDH and glutamine oxoglutarate aminotransferase (GOGAT in M. bovis BCG, despite their in vitro essentiality in M. tuberculosis. We could use these mutants to delineate the roles of GDH and GOGAT in mycobacterial nitrogen metabolism by using M. bovis BCG as a model for M. tuberculosis specifically. Here, we extended our investigation towards the involvement of GDH and GOGAT in other aspects of M. bovis BCG physiology, including the use of glutamate as a carbon source and resistance to known phagosomal stresses, as well as in survival inside macrophages. We find that gdh is indispensable for the utilization of glutamate as a major carbon source, in low pH environments and when challenged with nitric oxide. On the other hand, the gltBD mutant had increased viability under low pH conditions and was unaffected by a challenge with nitric oxide. Strikingly, GDH was required to sustain M. bovis BCG during infection of both murine RAW 264.7 and bone-marrow derived and macrophages, while GOGAT was not. We conclude that the catabolism of glutamate in slow growing mycobacteria may be a crucial function during infection of macrophage cells and demonstrate a novel requirement for M. bovis BCG GDH in the protection against acidic and nitrosative stress. These results provide strong clues on the role of GDH in intracellular survival of M. tuberculosis, in which the essentiality of the gdh gene complicates knock out studies making the study of the role of this enzyme in pathogenesis difficult.

  5. Tuberculin skin test distribution following a change in BCG vaccination policy.

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    Sei Won Lee

    Full Text Available BACKGROUND: Epidemiologic data regarding tuberculin skin test (TST responses are an important basis for TB control strategies. This study analyzed TST responses in Korea, which experienced a rapid change in BCG vaccination status. METHODS: TST responses in young adults were examined over 5 years. Participants with active TB lesions were excluded. RESULTS: A total of 5,552 participants were enrolled with median age of 21 years. When an induration diameter ≥10 mm was used as the criterion for a positive test, TST positivity fell (from 28.0% in 2005 to 15.3% in 2009; however, they remained steady when the criterion was ≥15-20 mm. A positive TST was associated with a personal or family of TB, the presence of a Bacille Calmette-Guérin (BCG scar, and age (odds ratio [95% confidence interval] = 4.03 [2.61-6.22], 2.91 [1.80-4.71], 1.50 [1.31-1.72], and 1.15 [1.09-1.20], respectively. Among these factors, the decrease of participants with BCG scars was the most prominent change, which appeared to be associated with the change of TST positivity rate. CONCLUSION: Overall, the rate of TST positivity in Korea decreased. However, this trend seems associated with the change of BCG vaccination strategy rather than successful control of LTBI. This study showed that change in BCG vaccination strategy can have great impact on TB epidemiologic survey based on TST.

  6. The Effect of BCG-PSN on T-cell Subsets and Cytokines in Vernal Conjunctivitis

    Institute of Scientific and Technical Information of China (English)

    胡军; 陈欢

    2002-01-01

    The effects of BCG-PSN on T-cell subsets and cytokines in vernal conjunctivitis were observed. The level of total IgE was quantitatively determined before and after treatment with BCGPSN by allergen diagnostic instrument in vitro. The content of T-cell subsets of peripheral blood and cytokine were determined by using indirect immune fluorescence method, and IL-4 and INF-γ were quantified by ELISA. The results showed that the level of total IgE was substantially reduced (P<0.01) after treatment in the BCG-PSN group. Meanwhile, CD8+ was decreased, CD4+ and CD4+/CD8+ratio elevated with significant differences (P<0. 05) as compared with pre-treatment results. The changes in total IgE, CD+8 ,CD4+ and CD4+/CD+8 ratio after treatment also presented significant differences (P<0. 05) between BCG-PSN group and routine treatment group. The level of IL-4 in serum declined (P<0. 05) after treatment in the BCG-PSN group, and INF-γ went up (P<0.05). IL-4and INF-γ in serum showed significant differences (P<0. 05) between two groups after treatment.It is concluded that BCG-PSN has a bi-directional immunoregulating effect. It can bring CD4+ and CD+8- into homeostasis, thereby preventing the occurrence of anaphylaxis. At the same time, BCGPSN can restrain Th2, decrease the synthesis of IL-4, switch the balance of Th1/Th2 to Th1 side,boost up the predominance of Th1 relatively, which is propitious to perennial stabilization and recov cry of vernal conjunctivitis.

  7. The glycosylated Rv1860 protein of Mycobacterium tuberculosis inhibits dendritic cell mediated TH1 and TH17 polarization of T cells and abrogates protective immunity conferred by BCG.

    Science.gov (United States)

    Satchidanandam, Vijaya; Kumar, Naveen; Jumani, Rajiv S; Challu, Vijay; Elangovan, Shobha; Khan, Naseem A

    2014-06-01

    We previously reported interferon gamma secretion by human CD4⁺ and CD8⁺ T cells in response to recombinant E. coli-expressed Rv1860 protein of Mycobacterium tuberculosis (MTB) as well as protection of guinea pigs against a challenge with virulent MTB following prime-boost immunization with DNA vaccine and poxvirus expressing Rv1860. In contrast, a Statens Serum Institute Mycobacterium bovis BCG (BCG-SSI) recombinant expressing MTB Rv1860 (BCG-TB1860) showed loss of protective ability compared to the parent BCG strain expressing the control GFP protein (BCG-GFP). Since Rv1860 is a secreted mannosylated protein of MTB and BCG, we investigated the effect of BCG-TB1860 on innate immunity. Relative to BCG-GFP, BCG-TB1860 effected a significant near total reduction both in secretion of cytokines IL-2, IL-12p40, IL-12p70, TNF-α, IL-6 and IL-10, and up regulation of co-stimulatory molecules MHC-II, CD40, CD54, CD80 and CD86 by infected bone marrow derived dendritic cells (BMDC), while leaving secreted levels of TGF-β unchanged. These effects were mimicked by BCG-TB1860His which carried a 6-Histidine tag at the C-terminus of Rv1860, killed sonicated preparations of BCG-TB1860 and purified H37Rv-derived Rv1860 glycoprotein added to BCG-GFP, but not by E. coli-expressed recombinant Rv1860. Most importantly, BMDC exposed to BCG-TB1860 failed to polarize allogeneic as well as syngeneic T cells to secrete IFN-γ and IL-17 relative to BCG-GFP. Splenocytes from mice infected with BCG-SSI showed significantly less proliferation and secretion of IL-2, IFN-γ and IL-17, but secreted higher levels of IL-10 in response to in vitro restimulation with BCG-TB1860 compared to BCG-GFP. Spleens from mice infected with BCG-TB1860 also harboured significantly fewer DC expressing MHC-II, IL-12, IL-2 and TNF-α compared to mice infected with BCG-GFP. Glycoproteins of MTB, through their deleterious effects on DC may thus contribute to suppress the generation of a TH1- and TH17-dominated

  8. The glycosylated Rv1860 protein of Mycobacterium tuberculosis inhibits dendritic cell mediated TH1 and TH17 polarization of T cells and abrogates protective immunity conferred by BCG.

    Directory of Open Access Journals (Sweden)

    Vijaya Satchidanandam

    2014-06-01

    Full Text Available We previously reported interferon gamma secretion by human CD4⁺ and CD8⁺ T cells in response to recombinant E. coli-expressed Rv1860 protein of Mycobacterium tuberculosis (MTB as well as protection of guinea pigs against a challenge with virulent MTB following prime-boost immunization with DNA vaccine and poxvirus expressing Rv1860. In contrast, a Statens Serum Institute Mycobacterium bovis BCG (BCG-SSI recombinant expressing MTB Rv1860 (BCG-TB1860 showed loss of protective ability compared to the parent BCG strain expressing the control GFP protein (BCG-GFP. Since Rv1860 is a secreted mannosylated protein of MTB and BCG, we investigated the effect of BCG-TB1860 on innate immunity. Relative to BCG-GFP, BCG-TB1860 effected a significant near total reduction both in secretion of cytokines IL-2, IL-12p40, IL-12p70, TNF-α, IL-6 and IL-10, and up regulation of co-stimulatory molecules MHC-II, CD40, CD54, CD80 and CD86 by infected bone marrow derived dendritic cells (BMDC, while leaving secreted levels of TGF-β unchanged. These effects were mimicked by BCG-TB1860His which carried a 6-Histidine tag at the C-terminus of Rv1860, killed sonicated preparations of BCG-TB1860 and purified H37Rv-derived Rv1860 glycoprotein added to BCG-GFP, but not by E. coli-expressed recombinant Rv1860. Most importantly, BMDC exposed to BCG-TB1860 failed to polarize allogeneic as well as syngeneic T cells to secrete IFN-γ and IL-17 relative to BCG-GFP. Splenocytes from mice infected with BCG-SSI showed significantly less proliferation and secretion of IL-2, IFN-γ and IL-17, but secreted higher levels of IL-10 in response to in vitro restimulation with BCG-TB1860 compared to BCG-GFP. Spleens from mice infected with BCG-TB1860 also harboured significantly fewer DC expressing MHC-II, IL-12, IL-2 and TNF-α compared to mice infected with BCG-GFP. Glycoproteins of MTB, through their deleterious effects on DC may thus contribute to suppress the generation of a TH1- and TH

  9. Client views, perception and satisfaction with immunisation services at Primary Health Care Facilities in Calabar, South-South Nigeria

    Institute of Scientific and Technical Information of China (English)

    Udonwa NE; Gyuse AN; Etokidem AJ; Ogaji DST

    2010-01-01

    Objective:To determine the degree of client satisfaction with immunisation services at Primary Health facilities in Calabar, Cross River State, Nigeria.Method: A semi-structured questionnaire was administered on 402 caregivers who were selected using systematic random sampling from four primary health centres. The four centres were randomly selected from the 19 health centres using the table of random numbers. Data obtained were analysed using Epi-Info software version 2002.Results: The majority of clients were dissatisfied with most aspects of care given at the Health Care Centres including long waiting time, accessibility of immunisation services, poor respect for clients' rights, especially to their dignity, health information and counseling on their medical needs.Conclusions:The study concludes that client satisfaction with immunization service in Calabar was low due to poor attitude of health care providers, long waiting time and lack of respect for clients' rights.

  10. Effects of active immunisation with myelin basic protein and myelin-derived altered peptide ligand on pain hypersensitivity and neuroinflammation.

    Science.gov (United States)

    Perera, Chamini J; Lees, Justin G; Duffy, Samuel S; Makker, Preet G S; Fivelman, Brett; Apostolopoulos, Vasso; Moalem-Taylor, Gila

    2015-09-15

    Neuropathic pain is a debilitating condition in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Specific myelin basic protein (MBP) peptides are encephalitogenic, and myelin-derived altered peptide ligands (APLs) are capable of preventing and ameliorating EAE. We investigated the effects of active immunisation with a weakly encephalitogenic epitope of MBP (MBP87-99) and its mutant APL (Cyclo-87-99[A(91),A(96)]MBP87-99) on pain hypersensitivity and neuroinflammation in Lewis rats. MBP-treated rats exhibited significant mechanical and thermal pain hypersensitivity associated with infiltration of T cells, MHC class II expression and microglia activation in the spinal cord, without developing clinical signs of paralysis. Co-immunisation with APL significantly decreased pain hypersensitivity and neuroinflammation emphasising the important role of neuroimmune crosstalk in neuropathic pain.

  11. Plasmid DNA Vaccine Co-Immunisation Modulates Cellular and Humoral Immune Responses Induced by Intranasal Inoculation in Mice.

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    Deborah F L King

    Full Text Available An effective HIV vaccine will likely require induction of both mucosal and systemic cellular and humoral immune responses. We investigated whether intramuscular (IM delivery of electroporated plasmid DNA vaccine and simultaneous protein vaccinations by intranasal (IN and IM routes could be combined to induce mucosal and systemic cellular and humoral immune responses to a model HIV-1 CN54 gp140 antigen in mice.Co-immunisation of DNA with intranasal protein successfully elicited both serum and vaginal IgG and IgA responses, whereas DNA and IM protein co-delivery did not induce systemic or mucosal IgA responses. Cellular IFNγ responses were preserved in co-immunisation protocols compared to protein-only vaccination groups. The addition of DNA to IN protein vaccination reduced the strong Th2 bias observed with IN protein vaccination alone. Luminex analysis also revealed that co-immunisation with DNA and IN protein induced expression of cytokines that promote B-cell function, generation of TFH cells and CCR5 ligands that can reduce HIV infectivity.These data suggest that while IN inoculation alone elicits both cellular and humoral responses, co-administration with homologous DNA vaccination can tailor these towards a more balanced Th1/Th2 phenotype modulating the cellular cytokine profile while eliciting high-levels of antigen-specific antibody. This work provides insights on how to generate differential immune responses within the same vaccination visit, and supports co-immunisation with DNA and protein by a mucosal route as a potential delivery strategy for HIV vaccines.

  12. The protective effect of immunisation against diphtheria, pertussis and tetanus (DPT) in relation to sudden infant death syndrome.

    Science.gov (United States)

    Essery, S D; Raza, M W; Zorgani, A; MacKenzie, D A; James, V S; Weir, D M; Busuttil, A; Hallam, N; Blackwell, C

    1999-08-01

    Epidemiological evidence indicates infants immunised against diphtheria, pertussis and tetanus (DPT) are at decreased risk of sudden infant death syndrome (SIDS). Asymptomatic whooping cough and pyrogenic toxins of Staphylococcus aureus have been implicated in the aetiology of SIDS. The objectives of the present study were: (1) to determine if the DPT vaccine induced antibodies cross-reactive with the staphylococcal toxins; (2) to determine if antibodies to the pertussis toxin (PT) and the staphylococcal toxins were present in the sera of women during late pregnancy; (3) to examine the effects of infant immunisation on levels of antibodies to PT and the staphylococcal toxins; (4) to assess the effects of changes in immunisation schedules in the UK on the incidence and age distribution of SIDS. Enzyme-linked immunosorbent assays (ELISA) were used to measure binding of rabbit or human IgG to the DPT vaccine, PT, toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins A (SEA), B (SEB) and C (SEC). Neutralisation activity of anti-DPT serum was assessed by a bioassay for induction of nitric oxide from human monocytes by the staphylococcal toxins. Anti-DPT serum bound to the DPT vaccine, PT and each of the staphylococcal toxins. It also reduced the ability of the four toxins to induce nitric oxide from monocytes. In pregnant women, levels of IgG to PT, SEC and TSST-1 decreased significantly in relation to increasing weeks of gestation while antibodies to SEA and SEB increased. In infants' sera there were significant correlations between levels of IgG bound to DPT and IgG bound to PT, TSST-1 and SEC but not SEA or SEB. Antibody levels to the toxins in infants declined with age; sera from infants antibodies cross-reactive with pyrogenic staphylococcal toxins implicated in many cases of SIDS. Passive immunisation of infants who have low levels of these antibodies might reduce further the numbers of these infant deaths.

  13. No influence of atopic diseases on antibody titres following tetanus, diphtheria and hepatitis B immunisation among adults.

    Science.gov (United States)

    Friedrich, N; Kramer, A; Mentel, R; Gürtler, L; John, U; Völzke, H

    2007-12-01

    Several studies have reported associations between reduced humoral immune response to vaccine antigens and diseases with modified reactions of the immune system. We have investigated the influence of atopic diseases on specific IgG levels to tetanus, diphtheria and hepatitis B (HB), following immunisation, in a general adult population. From the Study of Health in Pomerania, a total number of 3,920 subjects aged 20 to 79 years were included in the analyses. Information on immunisation history, as well as behavioural and socio-demographic characteristics were collected. Anti-tetanus IgG, anti-diphtheria IgG and anti-HBs IgG were measured by indirect enzyme-linked immunosorbent assay (ELISA). Odds ratios and 95% confidence intervals were calculated using logistic regression. Atopic diseases were reported by 14% of participants. Proportions of 67%, 34% and 10% had been vaccinated against tetanus, diphtheria and hepatitis B within the past ten years, respectively. Multi-variable analyses revealed no associations between the presence of atopic diseases and all of the three vaccine-specific antibody titres. We conclude that there is no reduced immune response related to antibody production following immunisations against tetanus, diphtheria and hepatitis B in adults with atopic diseases.

  14. Assessing vaccination coverage in infants, survey studies versus the Flemish immunisation register: achieving the best of both worlds.

    Science.gov (United States)

    Braeckman, Tessa; Lernout, Tinne; Top, Geert; Paeps, Annick; Roelants, Mathieu; Hoppenbrouwers, Karel; Van Damme, Pierre; Theeten, Heidi

    2014-01-09

    Infant immunisation coverage in Flanders, Belgium, is monitored through repeated coverage surveys. With the increased use of Vaccinnet, the web-based ordering system for vaccines in Flanders set up in 2004 and linked to an immunisation register, this database could become an alternative to quickly estimate vaccination coverage. To evaluate its current accuracy, coverage estimates generated from Vaccinnet alone were compared with estimates from the most recent survey (2012) that combined interview data with data from Vaccinnet and medical files. Coverage rates from registrations in Vaccinnet were systematically lower than the corresponding estimates obtained through the survey (mean difference 7.7%). This difference increased by dose number for vaccines that require multiple doses. Differences in administration date between the two sources were observed for 3.8-8.2% of registered doses. Underparticipation in Vaccinnet thus significantly impacts on the register-based immunisation coverage estimates, amplified by underregistration of administered doses among vaccinators using Vaccinnet. Therefore, survey studies, despite being labour-intensive and expensive, currently provide more complete and reliable results than register-based estimates alone in Flanders. However, further improvement of Vaccinnet's completeness will likely allow more accurate estimates in the nearby future.

  15. Political epidemiology: strengthening socio-political analysis for mass immunisation - lessons from the smallpox and polio programmes.

    Science.gov (United States)

    Taylor, S

    2009-01-01

    Control and reduction of infectious diseases is a key to attaining the Millennium Development Goals. An important element of this work is the successful immunisation, especially in resource-poor countries. Mass immunisation, most intensively in the case of eradication, depends on a combination of reliable demand (e.g. public willingness to comply with the vaccine protocol) and effective supply (e.g. robust, generally state-led, vaccine delivery). This balance of compliance and enforceability is, quintessentially, socio-political in nature - conditioned by popular perceptions of disease and risk, wider conditions of economic development and poverty, technical aspects of vaccine delivery, and the prevailing international norms regarding power relations between states and peoples. In the past 100 years, three out of six disease eradication programmes have failed. The explanations for failure have focused on biotechnical and managerial or financial issues. Less attention is paid to socio-political aspects. Yet socio-political explanations are key. Eradication is neither inherently prone to failure, nor necessarily doomed in the case of polio. However, eradication, and similar mass immunisation initiatives, which fail to address social and political realities of intervention may be. A comparison of the smallpox and polio eradication programmes illustrates the importance of disease-specific socio-political analysis in programme conceptualisation, design, and management.

  16. BCG-THERAPIE ET CANCER DE LA VESSIE : LA CARACTERISATION ET LA MODELISATION DE LA REPONSE IMMUNE AU BCG DANS LA VESSIE REVELENT DES STRATEGIES POUR L'AMELIORATION DE LA REPONSE ANTI-TUMORALE

    OpenAIRE

    Biot, Claire

    2012-01-01

    Intravesical instillation of bacillus Calmette-Guérin (BCG) for non-muscle invasive bladder cancer is one of the few examples of successful immunotherapy in the clinic, with 50-70% treatment response. While success of therapy is known to rely on repeated instillations of live BCG, administered as adjuvant therapy shortly after tumor resection, its precise mechanisms of action remain unclear. I established an experimental mouse model to study the dynamics of the immune response following intra...

  17. Enhanced and durable protective immune responses induced by a cocktail of recombinant BCG strains expressing antigens of multistage of Mycobacterium tuberculosis.

    Science.gov (United States)

    Liang, Jinping; Teng, Xindong; Yuan, Xuefeng; Zhang, Ying; Shi, Chunwei; Yue, Tingting; Zhou, Lei; Li, Jianrong; Fan, Xionglin

    2015-08-01

    Although Bacillus Calmette-Guérin (BCG) vaccine confers protection from Mycobacterium tuberculosis infection in children, its immune protection gradually wanes over time, and consequently leads to an inability to prevent the reactivation of latent infection of M. tuberculosis. Therefore, improving BCG for better control of tuberculosis (TB) is urgently needed. We thus hypothesized that recombinant BCG overexpressing immunodominant antigens expressed at different growth stages of M. tuberculosis could provide a more comprehensive protection against primary and latent M. tuberculosis infection. Here, a novel cocktail of recombinant BCG (rBCG) strains, namely ABX, was produced by combining rBCG::85A, rBCG::85B, and rBCG::X, which overexpressed respective multistage antigens Ag85A, Ag85B, and HspX of M. tuberculosis. Our results showed that ABX was able to induce a stronger immune protection than individual rBCGs or BCG against primary TB infection in C57BL/6 mice. Mechanistically, the immune protection was attributed to stronger antigen-specific CD4(+) Th1 responses, higher numbers of IFN-γ(+) CD4(+) TEM and IL-2(+) CD8(+) TCM cells elicited by ABX. These findings thus provide a novel strategy for the improvement of BCG efficacy and potentially a promising prophylactic TB vaccine candidate, warranting further investigation.

  18. Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection.

    Science.gov (United States)

    Xu, Zheng Zhong; Chen, Xiang; Hu, Ting; Meng, Chuang; Wang, Xiao Bo; Rao, Yan; Zhang, Xiao Ming; Yin, Yue Lan; Pan, Zhi Ming; Jiao, Xin An

    2016-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) is currently the only vaccine available for preventing tuberculosis (TB), however, BCG has varying success in preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A) strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. Our results indicated that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, and the Ag85A peptide-MHC complexes on draining lymph node dendritic cells of C57BL/6 mice infected with rBCG::Ag85A were detectable 4 h post-infection. The C57BL/6 mice infected with this strain had stronger antigen-specific interferon-gamma (IFN-γ) responses and higher antibody titers than those immunized with BCG, and the protective experiments showed that rBCG::Ag85A can enhance protection against Mycobacterium tuberculosis (M. tuberculosis) H37Rv infection compared to the BCG vaccine alone. Our results demonstrate the potential of rBCG::Ag85A as a candidate vaccine against TB.

  19. Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection.

    Science.gov (United States)

    Ma, Xiumin; Zhao, Hui; Zhang, Fengbo; Zhu, Yuejie; Peng, Shanshan; Ma, Haimei; Cao, Chunbao; Xin, Yan; Yimiti, Delixiati; Wen, Hao; Ding, Jianbing

    2016-01-01

    Cystic hydatid disease is a zoonotic parasitic disease caused by Echinococcus granulosus which is distributed worldwide. The disease is difficult to treat with surgery removal is the only cure treatment. In the high endemic areas, vaccination of humans is believed a way to protect communities from the disease. In this study we vaccinated BALB/c mice with rBCG-EgG1Y162, and then detected the level of IgG and IgE specifically against the recombinant protein by ELISA, rBCG-EgG1Y162 induced strong and specific cellular and humoral immune responses. In vitro study showed that rBCG-EgG1Y162 vaccine not only promote splenocytes proliferation but also active T cell. In addition, the rBCG-EgG1Y162 induced a protection in the mice against secondary infection of Echinococcus granulosus.

  20. Factors determining whether the parents accept BCG immunization of the new-born child in a high-income country

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte; Ammentorp, Jette; Kofoed, Poul-Erik

    Introduction: A large prospective randomised clinical trial in Denmark is planned to test the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood........ My focus for this project is decision making. Method: During the next year all parents planning to give birth at Kolding Hospital will be offered inclusion in the study . In the 2nd/3rd trimester they will receive a letter with information on the study and afterward the local Ph......' Connors 'Decisional Conflict scale' to compare decisional conflicts for the parents that accept BCG vaccination and parents who do not accept the BCG vaccination of their newborn child....

  1. Enhanced protective efficacy against tuberculosis provided by a recombinant urease deficient BCG expressing heat shock protein 70-major membrane protein-II having PEST sequence.

    Science.gov (United States)

    Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Mukai, Tetsu; Mitarai, Satoshi; Yamamoto, Saburo; Makino, Masahiko

    2016-12-07

    Enhancement of the T cell-stimulating ability of Mycobacterium bovis BCG (BCG) is necessary to develop an effective tuberculosis vaccine. For this purpose, we introduced the PEST-HSP70-major membrane protein-II (MMPII)-PEST fusion gene into ureC-gene depleted recombinant (r) BCG to produce BCG-PEST. The PEST sequence is involved in the proteasomal processing of antigens. BCG-PEST secreted the PEST-HSP70-MMPII-PEST fusion protein and more efficiently activated human monocyte-derived dendritic cells (DCs) in terms of phenotypic changes and cytokine productions than an empty-vector-introduced BCG or HSP70-MMPII gene-introduced ureC gene-depleted BCG (BCG-DHTM). Autologous human naïve CD8(+) T cells and naïve CD4(+) T cells were effectively activated by BCG-PEST and produced IFN-γ in an antigen-specific manner through DCs. These T cell activations were closely associated with phagosomal maturation and intraproteasomal protein degradation in antigen-presenting cells. Furthermore, BCG-PEST produced long-lasting memory-type T cells in C57BL/6 mice more efficiently than control rBCGs. Moreover, a single subcutaneous injection of BCG-PEST more effectively reduced the multiplication of subsequent aerosol-challenged Mycobacterium tuberculosis of the standard H37Rv strain and clinically isolated Beijing strain in the lungs than control rBCGs. The vaccination effect of BCG-PEST lasted for at least 6months. These results indicate that BCG-PEST may be able to efficiently control the spread of tuberculosis in human.

  2. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

    Directory of Open Access Journals (Sweden)

    O'Donnell Michael A

    2007-11-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Methods Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH. Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR was used to validate SSH-selected transcripts. Results Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5 and the p47GTPases (IIGTP1, IIGTP2, and TGTP. Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2, SPRR2G, GSTM5, and RSP 19. Conclusion Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially

  3. The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles)

    Science.gov (United States)

    Chambers, Mark A.; Aldwell, Frank; Williams, Gareth A.; Palmer, Si; Gowtage, Sonya; Ashford, Roland; Dalley, Deanna J.; Davé, Dipesh; Weyer, Ute; Salguero, Francisco J.; Nunez, Alejandro; Nadian, Allan K.; Crawshaw, Timothy; Corner, Leigh A. L.; Lesellier, Sandrine

    2017-01-01

    The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 108 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a 10-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a 10-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB or

  4. Effectiveness and cost-effectiveness of general immunisation of infants and young children with the heptavalent conjugated pneumococcal vaccine

    Directory of Open Access Journals (Sweden)

    Stürzlinger, Heidi

    2005-11-01

    Full Text Available Background: The European Agency for the Evaluation of Medicinal Products (EMEA granted market authorisation to the heptavalent pneumococcal vaccine Prevenar (Wyeth in the year 2001. The indication of Prevenar is the active immunisation of infants and young children under the age of two against invasive disease caused by Streptococcus pneumonia serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. At the time of this study the German vaccination scheme advises the immunisation with Prevenar only for children at high risk. Objectives: The objective of the study is first to determine the efficacy and effectiveness of the immunisation of all children with the heptavalent conjugated pneumococcal vaccine in Germany and second, whether a general recommendation for vaccination of all children would be cost-effective. Methods: A systematic literature search was performed in 29 relevant databases for the period of January 1999 to June 2004. Thus 1,884 articles were identified which were then assessed according to predefined selection criteria. Results: There is evidence for the medical effectiveness of Prevenar against invasive pneumococcal disease caused by the covered serotypes from a major double-blinded RCT undertaken in California. The vaccine shows lower values of effectiveness against otitis media and pneumonia. The values for effectiveness of the vaccine in Germany are below the data for California because of the different incidence of Serotypes. The cost-effectiveness rates for an immunisation of all children with Prevenar vary across different countries. One reason - besides different Health Systems - can be seen in the uncertainty about the duration of protection, another in the assumption on regional serotype coverage of the vaccine. From the healthcare payers' perspective a general vaccination of all children in Germany is not cost-effective, from a societal perspective the benefits from vaccination could prevail the cost. The actual price of the

  5. Vacina BCG: eficácia e indicações da vacinação e da revacinação BCG vaccine: efficacy and indications for vaccination and revaccination

    Directory of Open Access Journals (Sweden)

    Mauricio L. Barreto

    2006-07-01

    Full Text Available OBJETIVOS: Revisar aspectos relacionados ao efeito protetor da primeira e segunda doses da vacina BCG e discutir as suas principais indicações e contra-indicações. FONTES DOS DADOS: Utilizando o PubMed, foi realizada uma revisão sistemática da literatura abrangendo um período de, aproximadamente, 50 anos. Os estudos foram agrupados por tipo de desenho, apresentando-se separadamente os principais resultados de ensaios clínicos, estudos de caso-controle e meta-análises. Outros tópicos relevantes, como a BCG e HIV/AIDS, o uso do teste tuberculínico, aspectos relacionados à cicatriz vacinal e ao desenvolvimento de novas vacinas, dentre outros, foram também revistos. SÍNTESE DOS DADOS: A vacina BCG é utilizada desde 1921. Apesar disso, ainda apresenta controvérsias e aspectos não esclarecidos. O efeito protetor da primeira dose da vacina BCG contra a tuberculose na forma miliar ou na meningite é bastante significativa. No entanto, em relação à forma pulmonar, os resultados são discordantes, variando de ausência de efeito a níveis próximos a 80%. Há evidências de que uma segunda dose da BCG não aumenta o seu efeito protetor. Estudos demonstram proteção da vacina contra a hanseníase. Pesquisas sobre novas vacinas que, no futuro, poderão vir a substituir a BCG estão sendo realizadas. CONCLUSÕES:Apesar da expectativa de que, no futuro, venhamos a ter uma nova vacina para a tuberculose, no presente e ainda por muitos anos, a vacina BCG, apesar de suas deficiências, mantém-se como um importante instrumento nos esforços para controle dos efeitos danosos da tuberculose, sobretudo em países em que essa doença ocorre em médias e elevadas taxas de incidência.OBJECTIVES: To review the protective efficacy of the first and second doses of BCG vaccine and to assess its major indications and contraindications. SOURCES OF DATA: A systematic review of the literature was made by searching PubMed and selecting studies carried out

  6. Surveillance of adverse events following immunisation in Australia annual report, 2014.

    Science.gov (United States)

    Dey, Aditi; Wang, Han; Quinn, Helen E; Hill, Richard; Macartney, Kristine K

    2016-09-30

    This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) for 2014 reported to the Therapeutic Goods Administration for 2014 and describes reporting trends over the 15-year period 1 January 2000 to 31 December 2014. There were 3,087 AEFI records for vaccines administered in 2014; an annual AEFI reporting rate of 13.2 per 100,000 population. There was a decline of 5% in the overall AEFI reporting rate in 2014 compared with 2013. This decline in reported adverse events in 2014 compared with the previous year was mainly attributable to fewer reports following the human papillomavirus (HPV) vaccine as it was the 2nd year of the extension of the National HPV Vaccination Program to males. AEFI reporting rates for most vaccines were lower in 2014 compared with 2013. The most commonly reported reactions were injection site reaction (27%), pyrexia (18%), rash (16%), vomiting (9%), headache (7%), and syncope (5%). The majority of AEFI reports described non-serious events while 7% (n=211) were classified as serious. There were 5 deaths reported with no clear causal relationship with vaccination found.

  7. Intranasal immunisation with recombinant adenovirus vaccines protects against a lethal challenge with pneumonia virus of mice.

    Science.gov (United States)

    Maunder, Helen E; Taylor, Geraldine; Leppard, Keith N; Easton, Andrew J

    2015-11-27

    Pneumonia virus of mice (PVM) infection of BALB/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. This model system was used to investigate delivery of the internal structural proteins of PVM as a potential vaccination strategy to protect against pneumovirus disease. Replication-deficient recombinant human adenovirus serotype 5 (rAd5) vectors were constructed that expressed the M or N gene of PVM pathogenic strain J3666. Intranasal delivery of these rAd5 vectors gave protection against a lethal challenge dose of PVM in three different mouse strains, and protection lasted for at least 20 weeks post-immunisation. Whilst the PVM-specific antibody response in such animals was weak and inconsistent, rAd5N primed a strong PVM-specific CD8(+) T cell response and, to a lesser extent, a CD4(+) T cell response. These findings suggest that T-cell responses may be more important than serum IgG in the observed protection induced by rAd5N.

  8. Induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Jie Zhong

    Full Text Available Based on the life-time cost to the health care system, the Institute of Medicine has assigned the highest priority for a vaccine to control human cytomegalovirus (HCMV disease in transplant patients and new born babies. In spite of numerous attempts successful licensure of a HCMV vaccine formulation remains elusive. Here we have developed a novel chimeric vaccine strategy based on a replication-deficient adenovirus which encodes the extracellular domain of gB protein and multiple HLA class I & II-restricted CTL epitopes from HCMV as a contiguous polypeptide. Immunisation with this chimeric vaccine consistently generated strong HCMV-specific CD8(+ and CD4(+ T-cells which co-expressed IFN-gamma and TNF-alpha, while the humoral response induced by this vaccine showed strong virus neutralizing capacity. More importantly, immunization with adenoviral chimeric vaccine also afforded protection against challenge with recombinant vaccinia virus encoding HCMV antigens and this protection was associated with the induction of a pluripotent antigen-specific cellular and antibody response. Furthermore, in vitro stimulation with this adenoviral chimeric vaccine rapidly expanded multiple antigen-specific human CD8(+ and CD4(+ T-cells from healthy virus carriers. These studies demonstrate that the adenovirus chimeric HCMV vaccine provides an excellent platform for reconstituting protective immunity to prevent HCMV diseases in different clinical settings.

  9. Immunisation - Choice of host, adjuvants and boosting schedules with emphasis on polyclonal antibody production.

    Science.gov (United States)

    Delahaut, Philippe

    2017-03-01

    Polyclonal antibodies are frequently used as immunodiagnostic tools in fundamental research. They are also used for routine diagnostic purposes in human and veterinary medicine and for quality control procedures in the food-processing industry. The antibody is a major component of the detection system. It binds with the molecule to be identified. This conjugate is subsequently revealed by means of binding the antibody with a radio-isotope, a fluorescent substance, an enzyme inducing a color change, or a biosensor based analytical system. Polyclonal antibodies are also used for treatment purposes in various pathologies. They might have immunomodulating or anti-inflammatory properties. Snake venom, rabies and tetanus antisera are examples of a therapeutic application; immunosuppressive antithymocyte serum used in order to avoid rejection in organ transplantation is another example from human medicine. These therapeutic aids need hyperimmunisation of animals. Since these are subject to a certain number of interventions such as injections and blood samplings, animal welfare prescriptions have to be taken into account. The optimisation of the immunisation protocol allows for reducing the numbers of animals used as well as reducing stress and pain while obtaining high quality antibodies. This article describes the critical steps in polyclonal antibody production with a particular focus on the choice of the animal species, the age of the subjects, the injection protocol and the sampling times.

  10. Designing the Expanded Programme on Immunisation (EPI) as a service: Prioritising patients over administrative logic.

    Science.gov (United States)

    McKnight, Jacob; Holt, Douglas B

    2014-01-01

    Expanded Programme on Immunisation (EPI) vaccination rates remain well below herd immunity in regions of many countries despite huge international resources devoted to both financing and access. We draw upon service marketing theory, organisational sociology, development anthropology and cultural consumer research to conduct an ethnographic study of vaccination delivery in Jimma Zone, Ethiopia - one such region. We find that Western public health sector policies are dominated by an administrative logic. Critical failures in delivery are produced by a system that obfuscates the on-the-ground problems that mothers face in trying to vaccinate their children, while instead prioritising administrative processes. Our ethnographic analysis of 83 mothers who had not vaccinated their children reveals key barriers to vaccination from a 'customer' perspective. While mothers value vaccination, it is a 'low involvement' good compared to the acute daily needs of a subsistence life. The costs imposed by poor service - such as uncaring staff with class hostilities, unpredictable and missed schedules and long waits - are too much and so they forego the service. Our service design framework illuminates specific service problems from the mother's perspective and points towards simple service innovations that could improve vaccination rates in regions that have poor uptake.

  11. OPV strains circulation in HIV infected infants after National Immunisation Days in Bangui, Central African Republic

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    Menard Didier

    2010-05-01

    Full Text Available Abstract Background Humans are the only host of polioviruses, thus the prospects of global polio eradication look reasonable. However, individuals with immunodeficiencies were shown to excrete vaccine derived poliovirus for long periods of time which led to reluctance to prolong the vaccination campaign for fear of this end result. Therefore, we aimed to assess the duration of excretion of poliovirus after the 2001 National Immunization Days according to Human immunodeficiency virus status. Findings Fifty three children were enrolled. Sequential stool samples were collected in between National Immunisation Days rounds and then every month during one year. Children were classified into 2 groups: no immunodepression (n = 38, immunodepression (n = 15 according to CD4+ lymphocytes cells count. Thirteen poliovirus strains were isolated from 11 children: 5 Human immunodeficiency virus positive and 6 Human immunodeficiency virus negative. None of the children excreted poliovirus for more than 4 weeks. The restriction fragment length polymorphism analysis showed that all strains were of Sabin origin including a unique Polio Sabine Vaccine types 2 and 3 (S2/S3 recombinant. Conclusions From these findings we assume that Human immunodeficiency virus positive children are not a high risk population for long term poliovirus excretion. More powerful studies are needed to confirm our findings.

  12. PD-L2 induction on dendritic cells exposed to Mycobacterium avium downregulates BCG-specific T cell response.

    Science.gov (United States)

    Mendoza-Coronel, Elizabeth; Camacho-Sandoval, Rosa; Bonifaz, Laura C; López-Vidal, Yolanda

    2011-01-01

    The exposure to certain species of Nontuberculous Mycobacteria (NTM) can modulate the immune response induced by Mycobacterium bovis BCG. Mycobacterium avium has been postulated as a weak inducer of dendritic cell (DC) maturation. However, how the DC exposure to M. avium could contribute to the modulation of a BCG-specific CD4+ T cell response and the molecules involved remain unknown. Here, we exposed bone marrow-derived DCs (BMDCs) to M. avium either prior to exposure to BCG or as a unique stimulus. We found that M. avium induces high expression of PD-L2 (B7-DC) in BMDCs. This was dependent on IL-10 production through the TLR2-p38 MAPK signaling pathway. Exposure to M. avium prior to BCG results in BMDCs that do not express co-stimulatory molecules and pro-inflammatory cytokines, while the expression of PD-L2 and IL-10 was maintained. BMDCs exposed to M. avium impaired the activation of BCG-specific T cells through the PD-1: PD-L interaction. This suggests that a M. avium-induced phenotype in DCs might be implicated in the induction of mechanisms of tolerance that could impact the T cell response induced by BCG vaccination.

  13. Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

    Science.gov (United States)

    Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

    2016-02-10

    Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible.

  14. Recombinant BCG prime and PPE protein boost provides potent protection against acute Mycobacterium tuberculosis infection in mice.

    Science.gov (United States)

    Yang, Enzhuo; Gu, Jin; Wang, Feifei; Wang, Honghai; Shen, Hongbo; Chen, Zheng W

    2016-04-01

    Since BCG, the only vaccine widely used against tuberculosis (TB) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against TB. Prime-boost is proven to be a good strategy by inducing long-term protection. In this study, we tested the protective effect against Mycobacterium tuberculosis (Mtb) challenge of prime-boost strategy by recombinant BCG (rBCG) expressing PPE protein Rv3425 fused with Ag85B and Rv3425. Results showed that the prime-boost strategy could significantly increase the protective efficiency against Mtb infection, characterized by reduction of bacterial load in lung and spleen, attenuation of tuberculosis lesions in lung tissues. Importantly, we found that Rv3425 boost, superior to Ag85B boost, provided better protection against Mtb infection. Further research proved that rBCG prime-Rv3425 boost could obviously increase the expansion of lymphocytes, significantly induce IL-2 production by lymphocytes upon PPD stimulation, and inhibit IL-6 production at an early stage. It implied that rBCG prime-Rv3425 boost opted to induce Th1 immune response and provided a long-term protection against TB. These results implicated that rBCG prime-Rv3425 boost is a potent and promising strategy to prevent acute Mtb infection.

  15. Efeito do Mycobacterium bovis BCG, lipopolissacarideo bacteriano e hidrocortisona no desenvolvimento de imunidade ao Plasmodium berghei em camundongos

    Directory of Open Access Journals (Sweden)

    José J. Ferraroni

    1986-02-01

    Full Text Available Mycobacterium bovis (BCG aumenta significantemente o desenvolvimento da imunidade nos camundongos CFW, C57BL/6, C57BL/l0ScN e BALB/c (Nu/+ para os estágios eritrocitos do Plasmodium berghei. Camundongos tratados com BCG requerem menos ciclos de infecção com P. berghei e cura pelo Fansidar (pirimetamina + sulfadoxina para desenvolverem imunidade sólida a este parasita do que os controles. Contudo, os animais que receberam BCG 30 dias antes do início da imunização evidenciaram uma perda precoce da imunidade adquirida para o P. berghei, quando comparado com os animais que receberam BCG 14 dias antes ou que não receberam BCG. Assim, sendo, o BCG aumentada a indução na resposta imune do hospedeiro ao P. berghei no curso de infecções subseqüentes. O tratamento de camundongos CFW, BALB/c e C57BL/6 com lipopolissacarídeo bacteriano ou hidrocortisona faz com que os animais requeiram um número maior de ciclos de infecção e cura para tornarem-se imunes ao P. berghei que os controles. O tratamento dos camundongos C57BL/10ScN com hidrocortisona aboliu completamente a sua habilidade de sobrevida subseqüentes a ciclos de infecção com P. berghei e cura pelo Fansidar.

  16. Antitumor Effect of BCG on Growth of Transplanted Human Myeloid Leukemia HL-60 Cells in Nude Mice%卡介苗抑制裸鼠白血病移植瘤生长及抗肿瘤的实验研究

    Institute of Scientific and Technical Information of China (English)

    王媛媛; 王玲珍; 孙立荣

    2011-01-01

    This study was purposed to explore the anti-leukemia effect of bacillus calmette-guerin vaccine (BCG) on the human myeloid leukemia cell xenograft models.An animal model was established by inoculating the human myeloid leukemia HL-60 cells into the BALB/c (8 - 10 weeks of age) nude mice.The mice were randomly divided into two groups: control group and experimental group.Nude mice in control group were injected with physiological saline, while those of experimental group were given BCG and inactivated BCG respectively.The tumor growth was assayed by using caliper.The survival time of nude mice was determined.Necrotic extent and morphological changes of tumor were observed and examined by HE staining and immunohistochemical method.The results indicated that on 5th -7th days after tumor inoculated, 2 -3 mm tumor mass could be observed.The tumor volume increased over the time.HE staining of tumor tissues showed that there were different degrees of tumor necrosis in BCG group and inactivated BCG group.Immunohistochemistry results demonstrated that CD20 positive cells were obviously observed in the necrotic area of BCG group, compared with the control group and inactivated BCG group.It is concluded that human myeloid leukemia HL-60 cells have been successfully transplanted in nude mice, and the systemic metastasis occurs along with the prolongation of time.BCG inoculation can delay the tumor growth and prolong the survival time of nude mice with leukemia, suggesting that BCG has an antitumor effect.%本研究通过建立人白血病突变株细胞异种移植模型探讨卡介苗(bacillus calmette- guerin vaccine,BCG)的抗白血病作用.对8-10周龄的BALB/c裸鼠皮下接种1×107/ml人急性髓系白0细胞,于4-6天可形成皮下浸润的白血病裸鼠模型,随后将其分为2组:对照组和实验组.对照组于肿瘤内接种生理盐水,实验组又分为T1组(BCG组)、T2组(灭活的BCG组).观察各组裸鼠带瘤生存情况,以及通过对肿瘤组织

  17. Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg

    2011-01-01

    A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell) Bordetella pertussis (DTwP). In contrast, similar studies suggest that many African...... females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG) vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium...... phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence...

  18. Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie;

    2016-01-01

    MEASURES: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age Developmental assessment was available for 3453/4262 (81%). RESULTS......OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals...... was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....

  19. The clinical use of BCG-CWS and IL-2 for preventing recurrence of superficial bladder cancer%BCG-CWS联合IL-2预防浅表性膀胱癌术后复发

    Institute of Scientific and Technical Information of China (English)

    秦自科; 林奕中; 周志伟; 梅骅; 戴宇平

    2001-01-01

    Objective To study the therapeutic effects of intravesical instillation of cell wall skeleton of bacillus Calmett-Guerin ( BCG-CWS ) and interleukin 2 (IL-2 ) in preventing bladder cancers from recurring after local ablation.Methods 56 patients with superficial bladder cancers were randomized in using BCG-CWS and IL-2 or MMC for preventing bladder cancers from recurring after local ablation.Results The patients have been followed up for 12~30 months (mean 22.9 months).One patient had tumor recurrence in the group using BCG-CWS and IL-2 and five in the MMC group,the rates of tumor recurrence were 3.6%(1/28)and 18.0%(5/28) respectively, and the difference was statistically significant(P<0.05). There were obviously more side effects in intravesical instillation with MMC than BCG-CWS and IL-2.Conclusions Intravesical instillation of BCG-CWS and IL-2 is effective in preventing superficial bladder cancer from recurring after local ablation with fewer adverse effects.The ragimen is not only reliable but also safe.%目的 探讨卡介苗细胞壁骨架(BCG-CWS)+白细胞介素2(IL-2)膀胱灌注预防浅表性膀胱癌术后复发的临床效果。方法 56例浅表性膀胱癌局部手术后随机分为两组,每组28例。分别采用BCG-CWS加IL-2和单用丝裂霉素C(MMC)进行膀胱灌注。结果 56例随访12~30个月,平均22.9个月。BCG-CWS+IL-2组有1例肿瘤复发,MMC组有5例肿瘤复发,两组肿瘤复发率差别有显著性意义(P<0.05);MMC灌注组的毒副反应较BCG-CWS+IL-2组多。结论 BCG-CWS联合IL-2预防浅表性膀胱癌术后复发疗效较好,副反应少,临床使用安全可靠。

  20. Ureteric angioplasty balloon placement to increase localised dosage of BCG for renal pelvis TCC.

    LENUS (Irish Health Repository)

    Forde, J C

    2012-03-01

    Endoscopic percutaneous resection of a renal pelvis transitional cell carcinoma (TCC) is a viable treatment option in those who would be rendered dialysis dependent following a nephroureterectomy. We report endoscopic percutaneous resection of an upper tract TCC recurrence in a single functioning kidney followed by antegrade renal pelvis BCG instillation with novel placement of inflated angioplasty balloon in the ureter to help localise its effect.

  1. "PRESUMED SYSTEMIC BACILLE CALMETTE-GUÉRIN DISEASE AFTER BCG VACCINATION: REPORT OF A CLINICAL CASE "

    Directory of Open Access Journals (Sweden)

    P. Tabatabaie

    2006-08-01

    Full Text Available BCG (bacille Calmette–Guérin vaccine is administered worldwide to prevent severe forms of tuberculosis. It is considered to be safe; however, occasional complications are seen. The most serious complication is BCGosis. We report a case of BCGosis with granulomatous hepatitis and acid-fast bacilli in liver and spleen. We treated the patient with antituberculosis drugs without any response to treatment.

  2. Application of RAD-BCG calculator to Hanford's 300 area shoreline characterization dataset

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, Ernest J.; Poston, Ted M.; Tiller, Brett L.; Patton, Gene W.

    2003-07-01

    Abstract. In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy’s Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwest National Laboratory’s Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RAD-BCG Calculator. The RAD-BCG Calculator, a computer program that uses an Excel® spreadsheet and Visual Basic® software, showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RAD-BCG-Calculator’s site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program’s kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RAD-BCG Calculator results to be conservative, which is appropriate for screening purposes.

  3. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Science.gov (United States)

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

    1993-01-01

    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

  4. Ultrastructural characteristics of type A epithelioid cells during BCG-granulomatosis and treatment with lysosomotropic isoniazid.

    Science.gov (United States)

    Shkurupii, V A; Kozyaev, M A; Nadeev, A P

    2006-04-01

    We studied BCG-granulomas, their cellular composition, and ultrastructure of type A epithelioid cells in the liver of male BALB/c mice with spontaneous granulomatous inflammation. The animals received free isoniazid or isoniazid conjugated with lysosomotropic intracellularly prolonged matrix (dialdehyde dextran, molecular weight 65-75 kDa). Lysosomotropic isoniazid was accumulated in the vacuolar apparatus of epithelioid cells and produced a stimulatory effect on plastic processes in these cells.

  5. bcgTree: automatized phylogenetic tree building from bacterial core genomes.

    Science.gov (United States)

    Ankenbrand, Markus J; Keller, Alexander

    2016-10-01

    The need for multi-gene analyses in scientific fields such as phylogenetics and DNA barcoding has increased in recent years. In particular, these approaches are increasingly important for differentiating bacterial species, where reliance on the standard 16S rDNA marker can result in poor resolution. Additionally, the assembly of bacterial genomes has become a standard task due to advances in next-generation sequencing technologies. We created a bioinformatic pipeline, bcgTree, which uses assembled bacterial genomes either from databases or own sequencing results from the user to reconstruct their phylogenetic history. The pipeline automatically extracts 107 essential single-copy core genes, found in a majority of bacteria, using hidden Markov models and performs a partitioned maximum-likelihood analysis. Here, we describe the workflow of bcgTree and, as a proof-of-concept, its usefulness in resolving the phylogeny of 293 publically available bacterial strains of the genus Lactobacillus. We also evaluate its performance in both low- and high-level taxonomy test sets. The tool is freely available at github ( https://github.com/iimog/bcgTree ) and our institutional homepage ( http://www.dna-analytics.biozentrum.uni-wuerzburg.de ).

  6. [Generalized BCG infection after intravesical instillations of Calmette-Guerin bacillus].

    Science.gov (United States)

    de Saint Martin, L; Boiron, C; Poveda, J D; Herreman, G

    1993-10-02

    BCG has been disappointing as immunotherapy of numerous cancers, but it has been clinically successful in the intravesical treatment of bladder carcinomas sparing the muscle coat; it has indeed become the reference treatment for this type of cancer. However, complications are repeatedly reported, including generalized BCGitis. We report such a case with positive BCG culture. From the cases already published there emerges a homogeneous and often subacute clinical presentation suggestive of an ordinary pathogen. Bacteriology is not very helpful, even when recent techniques are used, and therefore the diagnosis rests on the context and, when samples are taken, on suggestive histological findings. To discuss the physiopathology of BCGitis--generalized immune reaction or multifocal BCG proliferation--is not useless since treatment depends on it. It is probable that these 2 mechanisms working together can be incriminated justifying the prescription of both antibiotics and corticosteroids. When this is done, the prognosis seems to be favourable in most patients. Yet a strict respect of contra-indications and a very careful subsequent radiotherapy should reduce the risks.

  7. New Recombinant Mycobacterium bovis BCG Expression Vectors: Improving Genetic Control over Mycobacterial Promoters

    Science.gov (United States)

    Kanno, Alex I.; Goulart, Cibelly; Rofatto, Henrique K.; Oliveira, Sergio C.; Leite, Luciana C. C.

    2016-01-01

    The expression of many antigens, stimulatory molecules, or even metabolic pathways in mycobacteria such as Mycobacterium bovis BCG or M. smegmatis was made possible through the development of shuttle vectors, and several recombinant vaccines have been constructed. However, gene expression in any of these systems relied mostly on the selection of natural promoters expected to provide the required level of expression by trial and error. To establish a systematic selection of promoters with a range of strengths, we generated a library of mutagenized promoters through error-prone PCR of the strong PL5 promoter, originally from mycobacteriophage L5. These promoters were cloned upstream of the enhanced green fluorescent protein reporter gene, and recombinant M. smegmatis bacteria exhibiting a wide range of fluorescence levels were identified. A set of promoters was selected and identified as having high (pJK-F8), intermediate (pJK-B7, pJK-E6, pJK-D6), or low (pJK-C1) promoter strengths in both M. smegmatis and M. bovis BCG. The sequencing of the promoter region demonstrated that it was extensively modified (6 to 11%) in all of the plasmids selected. To test the functionality of the system, two different expression vectors were demonstrated to allow corresponding expression levels of the Schistosoma mansoni antigen Sm29 in BCG. The approach used here can be used to adjust expression levels for synthetic and/or systems biology studies or for vaccine development to maximize the immune response. PMID:26850295

  8. Is tuberculin testing before BCG vaccination necessary for children over three months of age?

    LENUS (Irish Health Repository)

    Hennessy, B

    2008-03-01

    In July 2007 Irish national policy changed such that children aged 3 months to 6 years no longer routinely require tuberculin (Mantoux) skin testing prior to BCG vaccination. Previous to that a tuberculin test was required in all children in this age group pre vaccination. While the previous policy was in place this study was conducted to assess the value of this test. The observation that children are frightened by the test (an injection into the skin) prompted the study. The author conducted a retrospective study of the results of 1,854 tuberculin tests performed as a prerequisite to BCG vaccination and found that only 0.7% of children had a positive test result (induration > 5mm). None of 107 children < 6 years of age tested positive. Those > 12 years were more likely to test positive than younger children (1.09% vs 0.4% respectively, p < 0.05). This study suggests that testing young children before BCG vaccination has a low yield of positive results and adds little to the detection of latent or active TB.

  9. Effects of berberine hydrochloride on CYP450 total content and expression in BCG-induced immune hepatic injury in mice and its possible mechanism

    Institute of Scientific and Technical Information of China (English)

    XinWANG; DanLI; Jun-jieZHANG; Xiu-yunBU; Guo-liangZHANG

    2004-01-01

    AIM:To investigate effects of berberine hydrochloride on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice and its possible mechanism. METHODS: Immunological liver injury was induced by intravenous injection of Mycobacterium bovis bacillus Calmette-Guerin (BCG, 125 mg/kg) in BALB/c mice. After one week stimulated by BCG,berberine hydrochloride (10, 25, 50, 75, and 100 mg/kg,respectively, qid 7 d) was administrated by intragastric

  10. Studies of monocytopoiesis in patients with malignant disease and after imunostimulation with BCG, using /sup 3/H-thymidine as a DNA-label

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, E.; Meuret, G.; Waldermann, F.; Hoffmann, G.

    1982-04-01

    Monocytopoiesis and blood monocytes were investigated in patients with Hodgkin's disease, non-Hodgkin lymphomas, mycosis fungoides, breast cancer or melanoma. The investigation was carried out before surgery and just before each application of BCG. Monocyte production was increased in untreated patients. Postoperative prophylactic BCG-vaccination gave rise to increased proliferation activity. However monocyte production returned to normal between the 4th and 6th month of BCG immunotherapy. These results indicate that monocytopoiesis is stimulated by human tumors. BCG immunostimulation is able to increase proliferation activity during the first month of treatment only.

  11. Adverse events following primary and secondary immunisation with whole-cell pertussis: a systematic review protocol

    Science.gov (United States)

    Patterson, Jenna; Kagina, Benjamin M; Gold, Michael; Hussey, Gregory D; Muloiwa, Rudzani

    2017-01-01

    Introduction Pertussis is a contagious respiratory illness caused by the bacterium Bordetella pertussis. Two types of vaccines are currently available against the disease: whole-cell pertussis (wP) and acellular pertussis (aP). With the shift of high-income countries from wP to aP as a result of adverse events following immunisation (AEFI), an upsurge in reported cases of pertussis has been noticed. Owing to this, it is proposed to use wP as a prime and aP for boost vaccination strategy. However, a comparison of the AEFI with the first doses of wP and aP are not clearly documented. Methods and analysis The primary outcomes of interest are AEFI with dose 1 of wP, subsequent doses of wP and dose 1 of aP. As a secondary outcome frequency of AEFI with wP will be compared with the AEFI of doses 2 and 3 of wP and dose 1 of aP. Electronic databases will be searched and two authors will screen the titles and abstracts of the output. Full texts will then be independently reviewed by the first author and two other authors. Qualifying studies will then be formally assessed for quality and risk of bias using a scoring tool. Following standardised data extraction, statistical analysis will be carried out using STATA. Where data are available, subgroup analyses will be performed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be followed in reporting the findings of the systematic review and meta-analysis. Ethics and dissemination No ethics approval is required as the systematic review will use only published data already in the public domain. Findings will be disseminated through publication in a peer-reviewed journal. Trial registration number This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42016035809. PMID:28122832

  12. Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes.

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    Monica Poggianella

    Full Text Available Dengue virus (DENV infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.

  13. Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes.

    Science.gov (United States)

    Poggianella, Monica; Slon Campos, José L; Chan, Kuan Rong; Tan, Hwee Cheng; Bestagno, Marco; Ooi, Eng Eong; Burrone, Oscar R

    2015-01-01

    Dengue virus (DENV) infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII) of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE) in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.

  14. A New Recombinant BCG Vaccine Induces Specific Th17 and Th1 Effector Cells with Higher Protective Efficacy against Tuberculosis

    Science.gov (United States)

    da Costa, Adeliane Castro; Costa-Júnior, Abadio de Oliveira; de Oliveira, Fábio Muniz; Nogueira, Sarah Veloso; Rosa, Joseane Damaceno; Resende, Danilo Pires; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2014-01-01

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials. PMID:25398087

  15. A booster vaccine expressing a latency-associated antigen augments BCG induced immunity and confers enhanced protection against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bappaditya Dey

    Full Text Available BACKGROUND: In spite of a consistent protection against tuberculosis (TB in children, Mycobacterium bovis Bacille Calmette-Guerin (BCG fails to provide adequate protection against the disease in adults as well as against reactivation of latent infections or exogenous reinfections. It has been speculated that failure to generate adequate memory T cell response, elicitation of inadequate immune response against latency-associated antigens and inability to impart long-term immunity against M. tuberculosis infections are some of the key factors responsible for the limited efficiency of BCG in controlling TB. METHODS/PRINCIPAL FINDINGS: In this study, we evaluated the ability of a DNA vaccine expressing α-crystallin--a key latency antigen of M. tuberculosis to boost the BCG induced immunity. 'BCG prime-DNA boost' regimen (B/D confers robust protection in guinea pigs along with a reduced pathology in comparison to BCG vaccination (1.37 log(10 and 1.96 log(10 fewer bacilli in lungs and spleen, respectively; p<0.01. In addition, B/D regimen also confers enhanced protection in mice. Further, we show that B/D immunization in mice results in a heightened frequency of PPD and antigen specific multi-functional CD4 T cells (3(+ simultaneously producing interferon (IFNγ, tumor necrosis factor (TNFα and interleukin (IL2. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of α-crystallin based B/D regimen over BCG. Our study, also demonstrates that protection against TB is predictable by an increased frequency of 3(+ Th1 cells with superior effector functions. We anticipate that this study would significantly contribute towards the development of superior booster vaccines for BCG vaccinated individuals. In addition, this regimen can also be expected to reduce the risk of developing active TB due to reactivation of latent infection.

  16. Is there a correlation between the size of the BCG scar and renal scar of urinary tract infections in children?

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    Salih Kavukçu

    2013-03-01

    Full Text Available Objective: Pyelonephritis cause cellular death, and developmentof scars in kidneys. The aim of this study is todemonstrate a correlation (if any between renal scar, andsize of the scar induced by BCG vaccine in children whohad experienced urinary tract infections. In case of detectionof any correlation, BCG scar formation can be usedas a determinative marker of renal scars, which developfollowing urinary tract infection.Methods: Patients with a history of urinary tract infectionat least 4 months old who had undergone 99mTcDMSAscanning were included in this study. Vertical and horizontaldiameters of BCG scars of the patients in the studygroup were measured. For statistical analysis the greatestdiameter was taken into consideration, and the patientswere divided into 2 subgroups based on the greatest diameterof their BCG scars (Subgroups 1, ≤5 mm, and 2,>5 mm. The patients were also evaluated in 2 groupsas those with (Group 1 or without (Group 2 scars. Bothgroups were compared with subgroups with the largestscar diameters of ≤ 5mm or >5 mmResults: Study population included 108 (82 girls patients.DMSA detected scars in a total of 51 patients.Mean ages of the patients with and without scars were notdifferent (p=0.414. No significant difference was found insize of the BCG scars between renal scar positive andnegative groups (p>0.05.Conclusion: No correlation was found between developmentof renal scar and the size of BCG scar in childrenafter urinary tract infection. J Clin Exp Invest 2013; 4 (1:8-12Key words: BCG scar, renal scar, urinary tract infection,children

  17. Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

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    Dace Skrastina

    Full Text Available Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs formed by recombinant full-length Hepatitis B virus core (HBc protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.

  18. The use of supplementary immunisation activities to improve uptake of current and future vaccines in low-income and middle-income countries: a systematic review protocol

    Science.gov (United States)

    Kagina, Benjamin M; Wiysonge, Charles S; Machingaidze, Shingai; Abdullahi, Leila H; Adebayo, Esther; Uthman, Olalekan A; Hussey, Gregory D

    2014-01-01

    Introduction Immunisation coverage data in low-income and middle-income countries (LMICs) suggest that more strategies need to be implemented to achieve and sustain optimal vaccine uptake. Among possible strategies to improve immunisation coverage are supplementary immunisation activities (SIAs). We are therefore interested in conducting a systematic review to assess whether SIAs complement routine immunisation programmes to improve vaccination coverage and prevent disease outbreaks. Methods Our systematic review will focus on studies conducted in LMICs. With the help of an information specialist, we will search for eligible studies in PubMed, Web of Science, Scopus, Africa-Wide, Cochrane Library, WHOLIS, CINAHL, PDQ-Evidence as well as reference lists of relevant publications. Additionally, we will contact relevant organisations such as WHO and GAVI. Two authors will independently extract data from eligible studies and independently assess risk of bias by assessing the adequacy of study characteristics. The primary meta-analysis will use random effects models due to expected interstudies heterogeneity. Dichotomous data will be analysed using relative risk and continuous data using weighted mean differences (or standardised mean differences), both with 95% CIs. Discussion The findings from this systematic review will be discussed in the context of strengthening routine childhood immunisation services, routine adolescent immunisation services and introduction of future vaccines against tuberculosis and HIV/AIDS. Study strengths Unbiased selection of many studies conducted in different settings. This will strengthen the validity of the review results. Study limitations Heterogeneity of the study settings of the low-income, lower-middle-income and upper-middle-income countries as well as heterogeneity in study designs. PMID:24549166

  19. Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

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    Zenha EM

    2012-12-01

    Full Text Available Erika Muller Ramalho Zenha, Carlos Gustavo Wambier, Ana Lúcia Novelino, Thiago Antônio Moretti de Andrade, Maria Aparecida Nunes Ferreira, Marco Andrey Cipriani Frade, Norma Tiraboschi FossDivision of Dermatology, Ribeirão Preto Medical School, São Paulo University, São Paulo, BrazilIntroduction: The use of bacillus Calmette–Guérin (BCG has long been considered a stimulus for immune reactivity in leprosy household contacts. Probably, the combination of multidrug therapy with BCG could facilitate the clearance of leprosy bacilli in the host, reduce relapse rates, and shorten the duration of skin-smear positivity.Methods: To investigate the mechanism of action of BCG, a study involving 19 leprosy patients, eleven multibacillary (MB and eight paucibacillary, was performed to assess the in vitro production of interleukin (IL-10, interferon (IFN-γ, tumor necrosis factor (TNF-α, IL-6, and IL-17 in the supernatant of peripheral blood mononuclear cells, before and 30 days after inoculation with BCG intradermally (BCG-id. Peripheral blood mononuclear cells isolated by Ficoll–Hypaque gradient were cultivated with Concanavalin-A (Con-A, lipopolysccharides (LPS, or BCG. The supernatant was collected for ELISA quantification of cytokines. The immunohistochemistry of IFN-γ, IL-1, IL-10, IL-12, transforming growth factor (TGF-β, and TNF-α was carried out in biopsies of skin lesions of leprosy patients before and 30 days after inoculation of BCG-id. These patients were followed up for 5 years to assess the therapeutic response to multidrug therapy, the occurrence of leprosy reactions, and the results of bacterial index and anti-PGL-1 serology after the end of treatment. Results: The results showed increased production of cytokines after BCG-id administration in MB and paucibacillary leprosy patients. There was statistically higher levels of TNF-α (P = 0.017 in MB patients and of IL-17 (P = 0.008 and IFN-γ (P = 0.037 in paucibacillary patients

  20. Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

    Science.gov (United States)

    Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

    2011-12-15

    Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

  1. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

    Directory of Open Access Journals (Sweden)

    Ting-Yu Angela Liao

    Full Text Available Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

  2. Delayed childbearing.

    Science.gov (United States)

    Francis, H H

    1985-06-01

    In many Western nations, including England and Wales, Sweden, and the US, there is a current trend towards delayed childbearing because of women's pursuit of a career, later marriage, a longer interval between marriage and the 1st birth, and the increasing number of divorcees having children in a 2nd marriage. Wives of men in social classes I and II in England and Wales are, on average, having their 1st child at 27.9 years, 1.6 years later than in 1973, and in social classes IV and V, 1.0 years later than in 1973, at a mean age of 23.7 years. Consequently, the total period fertility rate for British women aged 30-34 years, 35-39 years, and 40 and over increased by 4%, 2%, and 4%, respectively, between 1982-83, in contrast to reductions of 2% and 3%, respectively, in the 15-19 year and 20-24 year age groups, with the 25-29-year-olds remaining static. The average maternal mortality for all parties in England and Wales during 1976-78 was 106/million for adolescents, 70.4/million for 20-24 year-olds, and 1162/million for those aged 40 years and older. The specific obstetric and allied conditions which increase with age are the hypertensive diseases of pregnancy, hemorrhage, pulmonary embolism, abortion, cardiac disease, caesarean section, ruptured uterus, and amniotic fluid embolism. The Swedish Medical Birth Registry of all live births and perinatal deaths since 1973 has shown that the risk of late fetal death is significantly greater in women aged 30-39 years than in those of the same parity and gravidity aged 20-24 years. The risk of giving birth to low birth weight babies preterm and at term and of premature labor are similarly increased. The early neonatal death rate also was increased for primigravidas and nulliparas in the 30-39 year age group but not in parous women. This is, in part, due to the rise in incidence of fetal abnormalities with advancing maternal age because of chromosomal and nonchromosomal anomalies. These also appear to be the cause of the

  3. Screening and Assessing 11 Mycobacterium tuberculosis Proteins as Potential Serodiagnostical Markers for Discriminating TB Patients from BCG Vaccinees

    Institute of Scientific and Technical Information of China (English)

    Guoqiang Zhang; Lingxia Zhang; Mingcheng Zhang; Linlin Pan; Fengyu Wang; Jun Huang; Guoli Li; Jun Yu; Songnian Hu

    2009-01-01

    Purified protein derivative(PPD)skin tests often yield poor specificity, so that to develop new serological antigens for distinguishing between Mycobacterium tu-berculosis infection and Bacille Calmette-Guerin(BCG)vaccination is a priority, especially for developing countries like China. We predicted the antigenicity for selected open reading frames(ORFs)based on the genome sequences of M. tu-berculosis H37Rv and M. bovis BCG, as well as their functions and differences of expression under different stimulus. The candidate ORFs were cloned from H37Rv sequences and expressed as recombinant proteins in Escherichia coll. We studied the serodiagnostic potential of 11 purified recombinants by using enzyme-linked immunosorbent assay(ELISA)and involving a cohort composed of 58 TB patients (34 males and 24 females), 8 healthy volunteers and 50 PPD-negative individuals before and after BCG vaccination. For all the 11 antigens, the median OD val-ues for the sera from TB patients were statistically significantly higher than those for PPD-negative individuals before or after BCG vaccination(P<0.01). They had at least 92% specificity in healthy controls and six seroantigens(Rv0251c, Rv1973, Rv2376c, Rv2537c, Rv2785c and Rv3873A)were never reported with seroantigenicities previously. Thus the approach combining comparative genomies, bioinformatics and ELISA techniques can be employed to identify new seroantigens distinguishing M. tuberculosis infection from BCG vaccination.

  4. The preparation of HL-60 cells vaccine expressing BCG heat shock protein 70 and detection of its immunogenicity in vitro.

    Science.gov (United States)

    Li, Xiao-Ling; Zhao, Yan-Xia; Sun, Li-Rong; Yang, Jing; Xu, Hui-Juan

    2012-10-01

    Gene-modified cell vaccines are the best way to achieve the immunotherapy for all types of acute leukemia. In this study, the recombinant eukaryotic expression vector (pDisplay-HSP70) of heat shock protein 70 (HSP70) of Bacille Calmette-Guérin (BCG) was constructed by amplifying the whole BCG HSP70 gene using polymerase chain reaction (PCR) and sub-cloning into the polyclone endonuclease sites in pDisplay. Then the HL-60 cell vaccine expressing the protein onto the cell surface was prepared by lipofectamine transfection and its anti-tumor effect and mechanism were further studied. Results showed that the fragment of BCG HSP70 was consistent with Mycobacterium tuberculosis HSP70 gene published in GeneBank. DNA sequencing showed that the recombinant vector was correctly constructed and named pDisplay-HSP70. After BCG HSP70 gene transfection, the yellow-green fluorescence on the HL-60 cells surface was observed under a fluorescence microscope. The immunogenicity of HSP70-transfected HL-60 cells exhibited upregulated proliferation of lymphocytes, increased cytokine secretion (IFN-γ) and enhanced killing activity. These results suggested that gene transfection of BCG HSP70 could significantly enhance the immunogenicity of HL-60 cells. It may be used as a suitable candidate gene-modified cell vaccine for cancer immunotherapy.

  5. Immunisation of mice against Taenia taeniaeformis using antigens prepared from T. pisiformis and T. hydatigena eggs or oncospheres.

    Science.gov (United States)

    Rickard, M D; Rajasekariah, G R; Mitchell, G F

    1981-01-01

    Experiments were carried out to investigation the degree of immunity stimulated against Taenia taeniaeformis infection in mice by prior administration of eggs or ultrasonically disrupted oncospheres of T. pisiformis or T. hydatigena. Sonicated oncospheral antigens were given either orally or by subcutaneous injection in Freund's complete adjuvant, and eggs were given orally. Three inbred strains of mice with varying degrees of innate resistance to initial infection with T. taeniaeformis were used in the experiments. These were the moderately resistant BALB/c, moderately susceptible CBA/H, and highly susceptible C3H/He strains. It was found that BALB/c mice developed high levels of immunity when immunised with either T. pisiformis or T. hydatigena eggs, or with sonicated oncospheres administered orally or parenterally. CBA/H mice developed moderate immunity, and C3H/He mice generally did not develop a satisfactory level of resistance. the implication of these findings with respect to immunisation of outbred animals against natural infection with larval cestodes using antigen prepared from the oncospheres of heterologous parasite species is discussed.

  6. Assessment of an oral Mycobacterium bovis BCG vaccine and an inactivated M. bovis preparation for wild boar in terms of adverse reactions, vaccine strain survival, and uptake by nontarget species

    OpenAIRE

    Beltrán-Beck, Beatriz; Romero, Beatriz; Sevilla, Iker A; Barasona, José A.; Garrido, Joseba M; González-Barrio, David; Díez-Delgado, Iratxe; Minguijón, Esmeralda; Casal, Carmen; Vicente, Joaquín; Gortázar, Christian; Aranaz, Alicia

    2014-01-01

    Wildlife vaccination is increasingly being considered as an option for tuberculosis control. We combined data from laboratory trials and an ongoing field trial to assess the risk of an oral Mycobacterium bovis BCG vaccine and a prototype heat-inactivated Mycobacterium bovis preparation for Eurasian wild boar (Sus scrofa). We studied adverse reactions, BCG survival, BCG excretion, and bait uptake by nontarget species. No adverse reactions were observed after administration of BCG (n = 27) or i...

  7. Modélisation des boucles d'immunisation magnétique des navires

    Science.gov (United States)

    Le Dorze, F.; Bongiraud, J. P.; Coulomb, J. L.; Meunier, G.; Brunotte, X.

    1998-02-01

    This paper presents the problem of the three-dimensional modeling of degaussing coils in ships with a finite elements method. We show that these current coils are so close to the ferromagnetic sheets of the ship that they require a local very fine mesh which would be unrealistic for the whole complex structure of a real ship. We propose an alternative to the expensive mesh refinement called "reduced scalar potential jump”. The idea is to previously solve the local problem by another method and to use the result in the whole FEM modelling. We present the method of implementation in the FEM software FLUX3D and comparative results on a simple geometry. Cet article présente le problème de la modélisation en trois dimensions des boucles d'immunisation des navires par la méthode des éléments finis. Nous montrons que ces boucles de courant sont si proches des tôles ferromagnétiques du navire que leur modélisation requiert un maillage localement très fin, ce qui est irréaliste pour la structure complexe d'un navire réel. Nous proposons une alternative à ce coûteux affinage du maillage, appelée "saut de potentiel réduit”. L'idée est de résoudre au préalable le problème local par une autre méthode que les éléments finis et d'utiliser le résultat dans la modélisation globale. Nous présentons la méthode utilisée pour l'implantation de cette technique dans le logiciel d'éléments finis FLUX3D, et des résultats comparatifs sur une géométrie simple.

  8. The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921-1933.

    Science.gov (United States)

    Bonah, Christian

    2005-12-01

    The anti-tuberculosis BCG (Bacille Calmette-Guérin) vaccine was conceived and developed between 1905 and 1921 at Pasteur Institutes in France. Between 1921 and A. Calmette's death in 1933, the vaccine went through a first period of national and international production and distribution for its use in humans. In France these activities were exclusively carried out by Calmette and his collaborators at the Pasteur Institute in Paris. Initially improvised production in a small room in the cellar gave way in 1931 to the construction of the spacious and magnificent 'New laboratories for research on tuberculosis and the preparation of the BCG' within the premises of the Pasteur Institute. Presentation and image-building of the vaccine in France insisted on the fact that the BCG was not a commercial specialty but distributed free of charge. The technical monopoly of its production nevertheless lay with the Paris Pasteur Institute and standardization of scientific proof of safety, efficacy and stability was dominated by that Institute in France. In contrast, the international production and distribution of the vaccine was entrusted and transferred, free of charge, to trustworthy laboratories outside France. Multiplication of producers and users led to an increased need for standardization. For this process the analysis distinguishes between the standardization of scientific proof concerning safety, efficacy and stability of the vaccine and standardization of its medical uses. Whereas standardization was rather successful in the inter-war period in France, the international efforts remained rather unsuccessful. Only after world war II under Scandinavian leadership and in the context of mass vaccination programs supported by the WHO and UNICEF was the international standardization effectively implemented and succeeded at least to some extend.

  9. BCG vaccination reduces risk of tuberculosis infection in vaccinated badgers and unvaccinated badger cubs.

    Directory of Open Access Journals (Sweden)

    Stephen P Carter

    Full Text Available Wildlife is a global source of endemic and emerging infectious diseases. The control of tuberculosis (TB in cattle in Britain and Ireland is hindered by persistent infection in wild badgers (Meles meles. Vaccination with Bacillus Calmette-Guérin (BCG has been shown to reduce the severity and progression of experimentally induced TB in captive badgers. Analysis of data from a four-year clinical field study, conducted at the social group level, suggested a similar, direct protective effect of BCG in a wild badger population. Here we present new evidence from the same study identifying both a direct beneficial effect of vaccination in individual badgers and an indirect protective effect in unvaccinated cubs. We show that intramuscular injection of BCG reduced by 76% (Odds ratio = 0.24, 95% confidence interval (CI 0.11-0.52 the risk of free-living vaccinated individuals testing positive to a diagnostic test combination to detect progressive infection. A more sensitive panel of tests for the detection of infection per se identified a reduction of 54% (Odds ratio = 0.46, 95% CI 0.26-0.88 in the risk of a positive result following vaccination. In addition, we show the risk of unvaccinated badger cubs, but not adults, testing positive to an even more sensitive panel of diagnostic tests decreased significantly as the proportion of vaccinated individuals in their social group increased (Odds ratio = 0.08, 95% CI 0.01-0.76; P = 0.03. When more than a third of their social group had been vaccinated, the risk to unvaccinated cubs was reduced by 79% (Odds ratio = 0.21, 95% CI 0.05-0.81; P = 0.02.

  10. BCG vaccine combined with dipyridamole in the treatment of HBV infection

    Institute of Scientific and Technical Information of China (English)

    Xu Wen Gao; Shi Ying Jia; Xue Mei Liu

    2000-01-01

    AIM To investigate the effect of BCG vaccine and dipyridamole in treating hepatitis B due to their anti-virus effects.METHODS Among 602 patients with positive HBeAg, 512 were allocated to the treatment group and 90patients to the control group. There was no significant difference in disease and age between the two groups.All the patients in the treatment group with no abnormal findings by chest X-ray fluoroscopy, whose localskin scleromata diameters were less than 7 mm after the 1:2000 OT test, were given BCG vaccine 0.1 mlintracutaneously at the deltoid once a month, and simultaneously took dipyridamole 50 mg twice a day forfour to eight months. The hepatic function, B-mode ultrasound and the five markers of hepatitis B wereroutinely examined before each injection. The results at one month after the last injection in the treatmentgroup were compared with those of the control group.RESULTS The recovery rates of hepatic functions and the rates of improvement of the symptoms and signsin the treatment group were better than those in the control group. The negative transformation rates ofHBeAg and the positive transformation rates of HBeAb were 60.3% and 31.6% in the treatment group vs.13.3% and 13.0% in the control group (P0.05. Test x2, x2=1.11, 0.22).CONCLUSION The application of BCG vaccine in combination with dipyridamole increased the negativetransformation rate of HBeAg and the positive transformation rate of HBeAb, improved the clinicalsymptoms, signs and hepatic function of the patients. These two drugs had significant anti-HBV effect andshowed good efficacy in the treatment of HBV infection.

  11. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

    KAUST Repository

    Abdallah, Abdallah M.

    2015-10-21

    Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

  12. Sex-differential effects on mortality of BCG and diphtheria-tetanus-pertussis vaccines in a rural area with high vaccination coverage

    DEFF Research Database (Denmark)

    Aaby, Peter; Nielsen, Jens; Benn, Christine S;

    2016-01-01

    and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine. RESULTS: BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person...

  13. Effect of milk fermentation by kefir grains and selected single strains of lactic acid bacteria on the survival of Mycobacterium bovis BCG.

    Science.gov (United States)

    Macuamule, C L S; Wiid, I J; van Helden, P D; Tanner, M; Witthuhn, R C

    2016-01-18

    Mycobacterium bovis that causes Bovine tuberculosis (BTB) can be transmitted to humans thought consumption of raw and raw fermented milk products from diseased animals. Lactic acid bacteria (LAB) used in popular traditional milk products in Africa produce anti-microbial compounds that inhibit some pathogenic and spoilage bacteria. M. bovis BCG is an attenuated non-pathogenic vaccine strain of M. bovis and the aim of the study was to determine the effect of the fermentation process on the survival of M. bovis BCG in milk. M. bovis BCG at concentrations of 6 log CFU/ml was added to products of kefir fermentation. The survival of M. bovis BCG was monitored at 12-h intervals for 72 h by enumerating viable cells on Middlebrook 7H10 agar plates enriched with 2% BD BACTEC PANTA™. M. bovis BCG was increasingly reduced in sterile kefir that was fermented for a period of 24h and longer. In the milk fermented with kefir grains, Lactobacillus paracasei subsp. paracasei or Lactobacillus casei, the viability of M. bovis BCG was reduced by 0.4 logs after 24h and by 2 logs after 48 h of fermentation. No viable M. bovis BCG was detected after 60 h of fermentation. Results from this study show that long term fermentation under certain conditions may have the potential to inactivate M. bovis BCG present in the milk. However, to ensure safety of fermented milk in Africa, fermentation should be combined with other hurdle technologies such as boiling and milk pasteurisation.

  14. PERBANDINGAN PENGGUNAAN MEDIA OGAWA PUSAT PENELITIAN PENYAKIT MENULAR DAN PERUM. BIO FARMA DALAM TES JUMLAH KUMAN VAKSIN BCG DI JAKARTA

    Directory of Open Access Journals (Sweden)

    Dyah W. Isbagio

    2012-09-01

    Full Text Available The aim of the study was to elaborate factors those might have played a role in the interlaboratory results discrepancies of the quality control for BCG vaccine. One hundred and nineteen samples of commercial BCG vaccine, produced by Bio Farma, had been put into extensive viability tests at Communicable Diseases Research Centre. The tests were done in a pair using Ogawa media prepared both by Bio Farma and by Communicable Diseases Research Centre. The Bio Farma's Ogawa medium revealed an average colony-count values of 1,529 x 106 particles/ ml^ while the Communicable Diseases Research Centre's Ogawa medium gave average figure of 1,504 x 10 particles/ml. As judged by student's paired t test, these results were not statistically significant. Apparently, the media used in the test were not responsible for the discrepancies of results of quality control for BCG vaccine.

  15. Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity

    DEFF Research Database (Denmark)

    Kleinnijenhuis, Johanneke; Quintin, Jessica; Preijers, Frank

    2013-01-01

    '. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months...... in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained...... changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses. © 2013 S. Karger AG, Basel....

  16. Enhanced and enduring protection against tuberculosis by recombinant BCG-Ag85C and its association with modulation of cytokine profile in lung.

    Directory of Open Access Journals (Sweden)

    Ruchi Jain

    Full Text Available BACKGROUND: The variable efficacy (0-80% of Mycobacterium bovis Bacille Calmette Guréin (BCG vaccine against adult tuberculosis (TB necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB. METHODS/PRINCIPAL FINDINGS: A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretory immuno-dominant protein of M. tuberculosis, was evaluated for its protective efficacy in guinea pigs against M. tuberculosis challenge by aerosol route. Immunization with rBCG85C resulted in a substantial reduction in the lung (1.87 log(10, p<0.01 and spleen (2.36 log(10, p<0.001 bacillary load with a commensurate reduction in pathological damage, when compared to the animals immunized with the parent BCG strain at 10 weeks post-infection. rBCG85C continued to provide superior protection over BCG even when post-challenge period was prolonged to 16 weeks. The cytokine profile of pulmonary granulomas revealed that the superior protection imparted by rBCG85C was associated with the reduced levels of pro-inflammatory cytokines - interleukin (IL-12, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, moderate levels of anti-inflammatory cytokine - transforming growth factor (TGF-beta along with up-regulation of inducible nitric oxide synthase (iNOS. In addition, the rBCG85C vaccine induced modulation of the cytokine levels was found to be associated with reduced fibrosis and antigen load accompanied by the restoration of normal lung architecture. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all

  17. The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette-Guérin (BCG) immunotherapy for urothelial carcinoma of the bladder.

    Science.gov (United States)

    Rosevear, Henry M; Lightfoot, Andrew J; O'Donnell, Michael A; Griffith, Thomas S

    2009-12-01

    Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 30 years of clinical experience with BCG, the therapy's mechanism has remained enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy have led to exciting discoveries regarding the potential role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic benefit of BCG immunotherapy. In this paper, we will review the scope of the disease, highlight our understanding of the role for BCG in urothelial carcinoma of the bladder, explain the recent discoveries regarding the role of neutrophils and TRAIL in therapy, and theorize on potential future areas of research.

  18. Eradication of established HPV16-transformed tumours after immunisation with recombinant Semliki Forest virus expressing a fusion protein of E6 and E7

    NARCIS (Netherlands)

    Daemen, T; Riezebos-Brilman, A; Bungener, L; Regts, J; Dontje, B; Wischut, J

    2003-01-01

    Previously, we described the efficacy of immunisation with recombinant Semliki Forest virus (SFV), expressing the human papillomavirus 16 (HPV) oncoproteins E6 and E7, in inducing HPV-specific CTLs and anti-tumour responses. Recently, we developed a novel recombinant SFV construct encoding a relativ

  19. Coverage of the English national human papillomavirus (HPV) immunisation programme among 12 to 17 year-old females by area-level deprivation score, England, 2008 to 2011.

    Science.gov (United States)

    Hughes, A; Mesher, D; White, J; Soldan, K

    2014-01-16

    The English national human papillomavirus (HPV) immunisation programme has offered vaccination to girls aged 12 years at the start of each school year since September 2008. A catch-up programme has offered vaccination to girls up to 18 years. Delivery is predominantly school-based, with some general practitioner (GP)-based immunisation. The relationship between HPV immunisation coverage and deprivation (index of multiple deprivation, IMD) was assessed by geographical area (N=151) for each school year offered the HPV vaccine between 2008 to 2011 using the Spearman’s rank correlation coefficient, and compared to that for adequate cervical screening of women aged 25 to 49 years. Coverage at age 12 showed no significant association with IMD at the area-level (p=0.12). Within the catch-up years, there was some suggestion of higher deprivation being associated with lower coverage. This was not significant for girls offered immunisation under 16 years (in compulsory education) (p=0.09), but was more marked and statistically significant for older girls (pimmunisation delivery appears to be successfully reducing inequalities in cervical cancer control at area-level. However, the catch-up cohorts above the age of compulsory education may face increased inequality. Further investigation is needed into individual-level factors associated with coverage.

  20. Non-invasive, epicutaneous immunisation with toxoid in deformable vesicles protects mice against tetanus, chiefly owing to a Th2 response.

    Science.gov (United States)

    Chopra, Amla; Cevc, Gregor

    2014-06-02

    A non-invasive, intra/transcutaneous immunisation of mice with a suitable combination of tetanus toxoid, ultradeformable vesicle (Transfersome®) carrier, and monophosphoryl lipid A adjuvant targets immuno-competent cells in a body and can protect 100% of the tested mice against an otherwise lethal (50×LD50) parenteral tetanus toxin challenge. The late immune response to the epicutaneously applied tetanus toxoid in such vesicles consists chiefly of circulating IgG1 and IgG2b antibody isotypes, indicative of a specific Th2 cellular response bias. Immunisations by subcutaneous injections moreover protect 100% of mice against a similar, otherwise lethal, dose of tetanus toxin. However, the immune response to transcutaneous and invasive immunisation differs. The latter elicits mainly IgG1 and IgG2b as well as IgG2a antibody isotypes, indicative of a mixed Th1/Th2 response. The cytokine response of the intra/transcutaneously and subcutaneously immunised mice reflects the difference in the organ-specific manner. IFN-γ concentration is appreciably increased in the draining lymph nodes and IL-10 in spleen. Since tetanus is a neutral antigen, both the Th1-specific IFN-γ and the Th-2 specific-IL-10 are observable.

  1. Distinct effector memory CD4+ T cell signatures in latent Mycobacterium tuberculosis infection, BCG vaccination and clinically resolved tuberculosis.

    Science.gov (United States)

    Adekambi, Toidi; Ibegbu, Chris C; Kalokhe, Ameeta S; Yu, Tianwei; Ray, Susan M; Rengarajan, Jyothi

    2012-01-01

    Two billion people worldwide are estimated to be latently infected with Mycobacterium tuberculosis (Mtb) and are at risk for developing active tuberculosis since Mtb can reactivate to cause TB disease in immune-compromised hosts. Individuals with latent Mtb infection (LTBI) and BCG-vaccinated individuals who are uninfected with Mtb, harbor antigen-specific memory CD4(+) T cells. However, the differences between long-lived memory CD4(+) T cells induced by latent Mtb infection (LTBI) versus BCG vaccination are unclear. In this study, we characterized the immune phenotype and functionality of antigen-specific memory CD4(+) T cells in healthy BCG-vaccinated individuals who were either infected (LTBI) or uninfected (BCG) with Mtb. Individuals were classified into LTBI and BCG groups based on IFN-γ ELISPOT using cell wall antigens and ESAT-6/CFP-10 peptides. We show that LTBI individuals harbored high frequencies of late-stage differentiated (CD45RA(-)CD27(-)) antigen-specific effector memory CD4(+) T cells that expressed PD-1. In contrast, BCG individuals had primarily early-stage (CD45RA(-)CD27(+)) cells with low PD-1 expression. CD27(+) and CD27(-) as well as PD-1(+) and PD-1(-) antigen-specific subsets were polyfunctional, suggesting that loss of CD27 expression and up-regulation of PD-1 did not compromise their capacity to produce IFN-γ, TNF-α and IL-2. PD-1 was preferentially expressed on CD27(-) antigen-specific CD4(+) T cells, indicating that PD-1 is associated with the stage of differentiation. Using statistical models, we determined that CD27 and PD-1 predicted LTBI versus BCG status in healthy individuals and distinguished LTBI individuals from those who had clinically resolved Mtb infection after anti-tuberculosis treatment. This study shows that CD4(+) memory responses induced by latent Mtb infection, BCG vaccination and clinically resolved Mtb infection are immunologically distinct. Our data suggest that differentiation into CD27(-)PD-1(+) subsets in

  2. Distinct effector memory CD4+ T cell signatures in latent Mycobacterium tuberculosis infection, BCG vaccination and clinically resolved tuberculosis.

    Directory of Open Access Journals (Sweden)

    Toidi Adekambi

    Full Text Available Two billion people worldwide are estimated to be latently infected with Mycobacterium tuberculosis (Mtb and are at risk for developing active tuberculosis since Mtb can reactivate to cause TB disease in immune-compromised hosts. Individuals with latent Mtb infection (LTBI and BCG-vaccinated individuals who are uninfected with Mtb, harbor antigen-specific memory CD4(+ T cells. However, the differences between long-lived memory CD4(+ T cells induced by latent Mtb infection (LTBI versus BCG vaccination are unclear. In this study, we characterized the immune phenotype and functionality of antigen-specific memory CD4(+ T cells in healthy BCG-vaccinated individuals who were either infected (LTBI or uninfected (BCG with Mtb. Individuals were classified into LTBI and BCG groups based on IFN-γ ELISPOT using cell wall antigens and ESAT-6/CFP-10 peptides. We show that LTBI individuals harbored high frequencies of late-stage differentiated (CD45RA(-CD27(- antigen-specific effector memory CD4(+ T cells that expressed PD-1. In contrast, BCG individuals had primarily early-stage (CD45RA(-CD27(+ cells with low PD-1 expression. CD27(+ and CD27(- as well as PD-1(+ and PD-1(- antigen-specific subsets were polyfunctional, suggesting that loss of CD27 expression and up-regulation of PD-1 did not compromise their capacity to produce IFN-γ, TNF-α and IL-2. PD-1 was preferentially expressed on CD27(- antigen-specific CD4(+ T cells, indicating that PD-1 is associated with the stage of differentiation. Using statistical models, we determined that CD27 and PD-1 predicted LTBI versus BCG status in healthy individuals and distinguished LTBI individuals from those who had clinically resolved Mtb infection after anti-tuberculosis treatment. This study shows that CD4(+ memory responses induced by latent Mtb infection, BCG vaccination and clinically resolved Mtb infection are immunologically distinct. Our data suggest that differentiation into CD27(-PD-1(+ subsets in LTBI is

  3. Socioeconomic disparities in coverage of full immunisation among children of adolescent mothers in India, 1990–2006: a repeated cross-sectional analysis

    Science.gov (United States)

    Kumar, Chandan; Singh, Prashant Kumar; Singh, Lucky; Rai, Rajesh Kumar

    2016-01-01

    Objective Studies have highlighted that children of adolescent (aged 15–19 years) mothers are likely to receive relatively poor healthcare. With an unacceptably high adolescent birth rate, India houses the highest number of adolescent mothers globally, putting children at risk of inadequate vaccination. This paper assesses trends and extent of socioeconomic disparities in the coverage of full immunisation among children of adolescent mothers in India. Design Repeated cross-sectional analytical study. Data sources 3 consecutive rounds of the National Family Health Survey (NFHS) conducted during 1992–1993, 1998–1999 and 2005–2006 were used. Besides, the required information is also extracted from the 2011 Indian Census. Participants Children (aged 12–23 months) of adolescent (aged 15–19 years) mothers. Sample inclusion criteria involved the last child of the adolescent eligible to avail full immunisation. Setting Nationally representative sample. Data analysis The Cochran-Armitage test, χ2 test and binary logistic regression methods were applied to attain the study objective. Results Between 1990 and 2006, a non-significant increase of 4 percentage points in full immunisation of children of adolescent mothers was estimated. During the same period, a large difference between the probability of children of adolescent mothers receiving full immunisation belonging to the least (predicted probability (PP): 0.196 in 1990–1993, and PP: 0.213 in 2003–2006) and the most (PP: 0.589 in 1990–1993, and PP: 0.645 in 2003–2006) socioeconomically privileged group was estimated, and this disparity persisted over the survey period. Conclusions During 1990–2006, an insufficient improvement in provision of full immunisation to children born to adolescent mothers was recorded. The study underscored the suboptimum immunisation of rural, illiterate and poor children of adolescent women. The programme and policymakers could focus on district-wise concentration

  4. Effectiveness of routine BCG vaccination on buruli ulcer disease: a case-control study in the Democratic Republic of Congo, Ghana and Togo.

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    Richard Odame Phillips

    2015-01-01

    Full Text Available The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis also called Bacillus Calmette-Guérin (BCG. Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD. The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD.The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors.After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31, sex (p = 0.24, age (p = 0.96, and presence of a BCG scar (p = 0.07 did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions.In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD.

  5. The maxBCG technique for finding galaxy clusters in SDSS data

    Science.gov (United States)

    Annis, J.; Kent, S.; Castander, F.; Eisenstein, D.; Gunn, J.; Kim, R.; Lupton, R.; Nichol, R.; Postman, M.; Voges, W.; SDSS Collaboration

    1999-12-01

    We present a new technique for finding galaxy clusters based on looking for a core of red, early type galaxies in the cluster center. These galaxies are known to have a small dispersion in color out to at least z=0.5. Further, the brightest of the ellipticals have near constant luminosity. In the maxBCG technique, one looks for objects whose appararent magnitudes and colors are consistent with their being brightest cluster galaxies (BCGs). If one presumes that any such object is a BCG, one can estimate a redshift and then search an area a half megaparsec around the galaxy for other galaxies that have the colors of the E/S0 ridgeline. One obtains a good estimate of the redshift by jointly minimizing the difference from the mean restframe brightest cluster galaxy properties while maximizing the number of galaxies in the E/S0 ridgeline. We have run this algoritm on the Abell clusters in the Sloan Digital Sky Survey commisioning data area with known redshifts, and find that the error in the estimated redshift z is only 0.02. This work was supported by the U.S. Department of Energy under contract No. DE-AC02-76CH03000.

  6. Mycobacterium leprae phenolglycolipid-1 expressed by engineered M. bovis BCG modulates early interaction with human phagocytes.

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    Guillaume Tabouret

    Full Text Available The species-specific phenolic glycolipid 1 (PGL-1 is suspected to play a critical role in the pathogenesis of leprosy, a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. Based on studies using the purified compound, PGL-1 was proposed to mediate the tropism of M. leprae for the nervous system and to modulate host immune responses. However, deciphering the biological function of this glycolipid has been hampered by the inability to grow M. leprae in vitro and to genetically engineer this bacterium. Here, we identified the M. leprae genes required for the biosynthesis of the species-specific saccharidic domain of PGL-1 and reprogrammed seven enzymatic steps in M. bovis BCG to make it synthesize and display PGL-1 in the context of an M. leprae-like cell envelope. This recombinant strain provides us with a unique tool to address the key questions of the contribution of PGL-1 in the infection process and to study the underlying molecular mechanisms. We found that PGL-1 production endowed recombinant BCG with an increased capacity to exploit complement receptor 3 (CR3 for efficient invasion of human macrophages and evasion of inflammatory responses. PGL-1 production also promoted bacterial uptake by human dendritic cells and dampened their infection-induced maturation. Our results therefore suggest that M. leprae produces PGL-1 for immune-silent invasion of host phagocytic cells.

  7. Health and economic outcomes of introducing the new MenB vaccine (Bexsero into the Italian routine infant immunisation programme.

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    Marcello Tirani

    Full Text Available In January 2013 a novel type of multicomponent protein-based vaccine against group B meningococcal disease was licensed by the European Medicines Agency. With the widespread use of the meningococcal serogroup C conjugate vaccines, serogroup B remains now the major cause of bacterial meningitis and septicaemia in young children in Europe. The aim of this study is to investigate the health and the economic outcomes of MenB vaccine introduction into the Italian routine mass vaccination programme.The present work is structured in two main parts. Firstly, we assess the epidemiological burden of group B meningococcal disease using official hospitalisation and notification data from two of the most populated Italian regions (Lombardia and Piemonte during a 6-year study period (2007-2012. Secondly, we evaluate the cost-effectiveness of the immunisation programme in Italy from the public health payer perspective under base case parameters assumptions and performing a comprehensive sensitivity analysis to assess the robustness and the uncertainty of our model results.MenB serotype is responsible for 59% of the 341 cases of Invasive Meningococcal Disease in Lombardia and Piemonte. Incidence rate for MenB infection is estimated to be 0.21/100,000/y resulting at the highest level in children ≤4 years of age. Although the new MenB vaccine can potentially prevent about one third of the disease cases in the Italian population, model results show this strategy is unlikely to be cost-effective (ICER value over €350,000/QALY with a vaccine that prevents disease only. These results are robust under most of the sensitivity scenarios except when allowing for lower discount rates.The introduction of the novel vaccine into the routine immunisation schedule needs to be carefully evaluated. The new MenB vaccine has the potential to reduce the disease burden at the population level. However, from the Italian Health Service perspective, the immunisation programme is

  8. Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960 Outra vacina, outra história: a vacinação de BCG contra tuberculose na Índia, 1948 a 1960

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    Niels Brimnes

    2011-02-01

    Full Text Available Through an examination of mass BCG vaccination against tuberculosis in India between 1948 and 1960 this article draws attention to the diversity of the history of vaccination. The features of vaccination campaigns often differed from those of the celebrated campaign to eradicate smallpox. Due to differences between smallpox and tuberculosis as well as between the vaccines developed against them, an analysis of BCG mass vaccination against tuberculosis seems particularly well suited for this purpose. Three points of difference are identified. First, in non-Western contexts BCG vaccination procedures were modified to a greater extent than vaccination against smallpox. Second, tuberculosis lacked the drama and urgency of smallpox and BCG vaccination campaigns suffered more from recruitment problems than did the more "heroic" smallpox eradication campaign. Third, the BCG vaccine was contested in medical circles and was much better suited than the vaccine against smallpox as a vehicle for the articulation of concerns about post-colonial modernization.Através da observação da vacinação em massa de BCG contra a tuberculose na Índia durante os anos de 1948 a 1960, este artigo chama a atenção para a diversidade da história da vacinação. As características das campanhas de vacinação geralmente diferem daquelas celebradas nas campanhas para erradicação da varíola. Devido às diferenças entre a varíola e a turberculose, assim como entre as vacinas desenvolvidas para combater essas doenças, uma análise da vacinação em massa de BCG contra a turberculose parece especialmente bem situada para essa proposta. Três pontos de diferença foram identificados. O primeiro é que em contextos não ocidentais os procedimentos da vacinação de BCG foram modificados em uma extensão maior do que a vacinação contra a varíola. Em segundo lugar, a tuberculose não tinha o drama e a urgência da varíola, e as campanhas de vacinação de BCG

  9. Prova tuberculínica, BCG oral e infecção tuberculosa em crianças menores de 5 anos Tuberculin test, oral BCG vaccine, and tuberculosis infection among children under five years of age

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    Marialda Höfling de Pádua Dias

    1978-12-01

    Full Text Available São relatados os resultados das provas tuberculínicas com PPD Rt23, 2 UT, em crianças menores de um ano e de um a 4 anos, matriculadas na Clínica Pediátrica do Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brasil, no período de 1971 a 1975. Em 665 crianças menores de um ano encontrou-se 3,15% de reatores fracos e 6,62% de reatores fortes e em 1.298 crianças de um a 4 anos, 0,69% de reatores fracos e 5,5% de reatores fortes. Nas mesmas crianças, foram estudadas as relações entre vacinação BCG oral prévia e positividade à prova tuberculínica nos 2 grupos etários considerados e nos quais se obteve a informação de vacinação anterior com BCG oral. Em 575 crianças menores de um ano e 1.113 de um a 4 anos encontrou-se associação positiva entre vacinação BCG oral prévia e positividade à prova tuberculínica. Analisando a relação entre o número de doses de BCG oral prévio e o resultado das provas tuberculínicas pelo método de Goodman, verificou-se que a proporção de crianças que tinham tomado 3 doses e mais de BCG oral e que apresentaram reação forte à prova tuberculínica é significantemente maior que a observada para os não reatores, fato esse não verificado para o grupo de um a 4 anos. Nas crianças que tomaram uma ou duas doses não foram encontradas diferenças estatisticamente significantes.Results of tuberculin reaction from PPD Rt 23, 2UT are reported on children under one year of age and children from one to four years of age who were registered in the Pediatric Clinics of the Hospital das Clinicas of the College of Medicine of the State University of São Paulo. The study was carried out from 1971 through 1975. In a group of 665 children under one year of age, 3.15% were weak reactors while 6.62% were strong reactors, and, in a group of 1298 children between one to four years of age, 0.69% were weak reactors while 5.5% were strong reactors. The relationship between prior BCG oral

  10. Isolation and identification of arabinose mycolates of Cell Wall Skeleton (CWS) derived from Mycobacterium bovis BCG Tokyo 172 (SMP-105).

    Science.gov (United States)

    Uenishi, Yuko; Kusunose, Naoto; Yano, Ikuya; Sunagawa, Makoto

    2010-03-01

    A unique hydrolysis method using a two-layer solution, consisting of diluted hydrochloric acid and toluene was developed to isolate whole arabinose mycolates from the cell wall skeleton of Mycobacterium bovis BCG Tokyo 172 (SMP-105) in order to reveal its pivotal role in enhancing immune responses against tumors.

  11. Developing the Biological Condition Gradient (BCG), as a Tool for Describing the Condition of US Coral Reefs

    Science.gov (United States)

    Understanding effects of human activity on coral reefs requires knowing what characteristics constitute a high quality coral reef and identifying measurable criteria. The BCG is a conceptual model that describes how biological attributes of coral reefs change along a gradient of ...

  12. The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.

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    Rolf Billeskov

    Full Text Available BACKGROUND: The current vaccine against tuberculosis (TB, BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10-15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. METHODS/FINDINGS: In the present study we show that the fusion protein HyVac4 (H4, consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb. Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. CONCLUSIONS/SIGNIFICANCE: H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials.

  13. A Comparative Study on the Effect of BCG-PSN and Thymopeptides on T-lymphocyte Subsets of Normal and Immunosuppressed Mice

    Institute of Scientific and Technical Information of China (English)

    邓云华; 陈映玲; 陈兴平; 李永喜; 周礼义

    2003-01-01

    To compare the effects of polysaccharide nucleic acid fraction of bacillus calmette guerin (BCG-PSN) and thymopeptides on T-lymphocytes of normal and immunosuppressed mice, CD4+ and CD8+ T-lymphocyte subsets of single nucleic cell in thymus, spleen and peripheral blood were detected successively by flow cytometry after application of BCG-PSN and thymopeptides. Meanwhile, CD4+/CD8+ ratio was also calculated. The results showed that both BCG-PSN and thymopeptides could decrease the proportion of CD4+ CD8+ T-lymphocyte subsets in the thymus, at the same time increase CD4+ T-lymphocyte, CD8+ T-lymphocyte proportion in the three tissues.The fluctuation in amplitude was greater in thymopeptides group than that in BCG-PSN group. It is concluded that acting location of thymopeptides is in thymus, its stimulating action is stronger than that of BCG-PSN, while BCG-PSN not only accelerates the differentiation in thymus, but also has some direct stimulation to peripheral CD4+ T-lymphocytes, and can maintain CD4+/CD8+ ratio within normal range. So, BCG-PSN is safer.

  14. Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

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    Joan Joseph

    2010-01-01

    Full Text Available Mycobacterium bovis Bacillus Calmette-Guérin (BCG as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261 and Mycobacteria spp. α-antigen promoter (in plasmid pJH222. Among 14 rBCG:HIV-1gp120 (pMV261 colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222 colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

  15. Histopathological, immunohistochemical and ultraestructural evaluation of inflammatory response in Arius genus fish under experimental inoculation of BCG

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    Ricardo Yuji Sado

    2008-10-01

    Full Text Available The aim of this study was to evaluate the inflammatory response kinetics after experimental inoculation with BCG in the primitive Arius sp. fish. The BCG was applied through the intramuscular injection in the caudal peduncular region, and the samples were collected for the analyses at days 1, 3, 7, 14, 21, and 33 post-injection. Acute phase inflammatory infiltrate was characterized by the predominant mononuclear cells, intersticial edema, and muscular tissue necrosis. As the inflammatory response evolved, a large number of multinuclear giant cells were formed containing the BCG. These giant cells were positive for the S100 protein at the histochemical analysis, which demonstrate the macrofage activity, confirmed by the ultra-structural analysis showing the lack of the cytoplasmic membrane enveloping the many nuclei within the giant cell. These results led to the conclusion that Arius sp. fish injected with the BCG showed a difuse inflammatory response characterized by a large number of mononuclear cells, absence of granuloma formation, and predominant giant cells.Avaliou-se a cinética da resposta inflamatória induzida experimentalmente com BCG em peixes primitivos pertencentes ao gênero Arius. Os animais foram inoculados com BCG por via intramuscular na região do pedúnculo caudal, sendo realizada a coleta do material nos tempos experimentais de 1, 3, 7, 14, 21 e 33 dias pós-inoculação. A fase aguda da resposta inflamatória se mostrou na forma de infiltrado inflamatório composto predominantemente por células mononucleares, edema intersticial e necrose de tecido muscular. À medida que o processo se desenvolveu, houve formação e aumento no número de células gigantes multinucleadas envolvendo o inóculo. Essas células gigantes, ao exame imunohistoquímico, apresentaram positividade à proteína S100 indicando ação de células macrofágicas, além da ultraestrutura apontar a ausência de membrana citoplasmática entre os in

  16. The impact of BCG vaccination on tuberculin skin test responses in children is age dependent: evidence to be considered when screening children for tuberculosis infection

    Science.gov (United States)

    Seddon, James A; Paton, James; Nademi, Zohreh; Keane, Denis; Williams, Bhanu; Williams, Amanda; Welch, Steven B; Liebeschutz, Sue; Riddell, Anna; Bernatoniene, Jolanta; Patel, Sanjay; Martinez-Alier, Nuria; McMaster, Paddy; Kampmann, Beate

    2016-01-01

    Background Following exposure to TB, contacts are screened to target preventive treatment at those at high risk of developing TB. The UK has recently revised its recommendations for screening and now advises a 5 mm tuberculin skin test (TST) cut-off irrespective of age or BCG status. We sought to evaluate the impact of BCG on TST responses in UK children exposed to TB and the performance of different TST cut-offs to predict interferon γ release assay (IGRA) positivity. Methods Children vaccination on TST positivity was evaluated in IGRA-negative children, as was the performance of different TST cut-offs to predict IGRA positivity. Results Of 422 children recruited (median age 69 months; IQR: 32–113 months), 300 (71%) had been vaccinated with BCG. BCG vaccination affected the TST response in IGRA-negative children less than 5 years old but not in older children. A 5 mm TST cut-off demonstrated good sensitivity and specificity in BCG-unvaccinated children, and an excellent negative predictive value but was associated with low specificity (62.7%; 95% CI 56.1% to 69.0%) in BCG-vaccinated children. For BCG-vaccinated children, a 10 mm cut-off provided a high negative predictive value (97.7%; 95% CI 94.2% to 99.4%) with the positive predictive value increasing with increasing age of the child. Discussion BCG vaccination had little impact on TST size in children over 5 years of age. The revised TST cut-off recommended in the recent revision to the UK TB guidelines demonstrates good sensitivity but is associated with impaired specificity in BCG-vaccinated children. PMID:27335104

  17. Outcomes of BCG Induction in High-Risk Non-Muscle-Invasive Bladder Cancer Patients (NMIBC): A Retrospective Cohort Study

    Science.gov (United States)

    Ghauri, Rashid; Ahmed, Monis J; Shah, Muhammad F; Nasir, Irfan ul Islam; Siddiqui, Jasim; Ahmed, Irfan; Mir, Khurram

    2017-01-01

    Non-muscle-invasive bladder cancer (NMIBC) is categorized into high-risk and low-risk groups. Although, bacillus Calmette-Guerin (BCG) is the recommended adjuvant therapy of high-risk bladder tumor, optimal schedule (induction versus maintenance) of this therapy is a subject of debate. The objective was to evaluate outcomes of induction BCG in high-risk NMIBC patients at Shaukat Khanum Memorial Cancer Hospital & Research Centre, Pakistan and retrospective cohort study conducted in the department of urology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Pakistan. Three-year disease-free survival and progression-free survival was the main outcome measure. Data of 68 high-risk (Ta and T1 with G3 or high-grade subtype) bladder cancer patients who underwent transurethral resection followed by six-weekly intravesical BCG instillation was included in the study. Recurrence was described as biopsy-proven bladder cancer; whereas the presence of muscle invasion was considered as progression. Disease-free survival and progression-free survival were defined as time intervals elapsed between the starting date of BCG instillation and recurrence or progression, respectively. Kaplan-Meier curve was employed to estimate the three-year study end-points. Disease-free survival at three years was observed to be 66.2% and progression-free survival at 86.8%. The use of induction BCG alone for high-risk patients of NMIBC is a viable option both in terms of effective disease-free and progression-free survival rates. PMID:28168135

  18. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

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    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  19. The mycobacterial DNA-binding protein 1 (MDP1 from Mycobacterium bovis BCG influences various growth characteristics

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    Maurischat Sven

    2008-06-01

    Full Text Available Abstract Background Pathogenic mycobacteria such as M. tuberculosis, M. bovis or M. leprae are characterised by their extremely slow growth rate which plays an important role in mycobacterial virulence and eradication of the bacteria. Various limiting factors influence the generation time of mycobacteria, and the mycobacterial DNA-binding protein 1 (MDP1 has also been implicated in growth regulation. Our strategy to investigate the role of MDP1 in mycobacterial growth consisted in the generation and characterisation of a M. bovis BCG derivative expressing a MDP1-antisense gene. Results The expression rate of the MDP1 protein in the recombinant M. bovis BCG containing the MDP1-antisense plasmid was reduced by about 50% compared to the reference strain M. bovis BCG containing the empty vector. In comparison to this reference strain, the recombinant M. bovis BCG grew faster in broth culture and reached higher cell masses in stationary phase. Likewise its intracellular growth in mouse and human macrophages was ameliorated. Bacterial clumping in broth culture was reduced by the antisense plasmid. The antisense plasmid increased the susceptibility of the bacteria towards Ampicillin. 2-D protein gels of bacteria maintained under oxygen-poor conditions demonstrated a reduction in the number and the intensity of many protein spots in the antisense strain compared to the reference strain. Conclusion The MDP1 protein has a major impact on various growth characteristics of M. bovis BCG. It plays an important role in virulence-related traits such as aggregate formation and intracellular multiplication. Its impact on the protein expression in a low-oxygen atmosphere indicates a role in the adaptation to the hypoxic conditions present in the granuloma.

  20. The Right Delay

    NARCIS (Netherlands)

    Datadien, A.H.R.; Haselager, W.F.G.; Sprinkhuizen-Kuyper, I.G.

    2011-01-01

    Axonal conduction delays should not be ignored in simulations of spiking neural networks. Here it is shown that by using axonal conduction delays, neurons can display sensitivity to a specific spatio-temporal spike pattern. By using delays that complement the firing times in a pattern, spikes can ar

  1. Curative effect of BCG-polysaccharide nuceic acid on atopic dermatitis in mice

    Institute of Scientific and Technical Information of China (English)

    Liu-Hui Wang; Ying Ye; Yi-Qun Zhang; Tao Xiao

    2014-01-01

    Objective:To explore the effect of bacilli Galmette-Gurin (BCG)-polysaccharide nuceic acid on atopic dermatitis in mice and its mechanism. Methods: Forty NC/Nga mice were selected and randomly divided into Group A (model group), Group B (dexamethasone treatment group), Group C (BCG polysaccharide nucleic acid treatment group) and Group D (control group) with 10 mice in each group. Atopic dermatitis model were constructed by applying 2, 4-dinitrochlorobenzene on the skin of the mice. Mice in Group D were treated with acetone solution (100μL) on the foot pad and abdomen after hair removal at the age of 7 weeks, then on ear skin at the age of 8-13 weeks. For mice in A, B and C groups, 100μL of acetone solution containing 2, 4-dinitrochlorobenzene was applied to the foot pad and the abdomen at the age of 7 weeks, then on ear skins at the age of 8 to 13 weeks. At the age of 7-13 weeks, mice in Group A and Group D were treated with 100μL saline (i.p.);mice were given dexamethasone (0.1 mL/kg, i.p.) every other day for 7 weeks in Group B;mice were treated with BCG polysaccharide nucleic acid (0.5 mg/kg, i.p.) every other day for 7 weeks in Group C. The ear thickness was measured every week and the scratching frequency was recorded 1 times for 10 min a week. The mice were sacrificed after the last administration of drugs. IgE, IL-4, IL-10, IL-12 and IFN-γin the plasma were detected using ELISA, and RT-PCR method was employed to detect the concentrations of IL-4, IL-10, IL-12 and IFN-γproteins. After HE staining, the lesion degree of inflammation in ear tissue was observed microscopically. Results:The ear thickness and scratching frequency of Group A were significantly higher than those in group B, C and D (P0.05);the concentrations of IgE, IL-4 and IL-10 in the plasma and the expression of IL-4, IL-10 mRNA in the spleen tissues of Group A, B and C were all significantly higher than those of Group D (P<0.05);the concentrations of plasma IL-12 and IFN-γ, and spleen

  2. The role of glutamine oxoglutarate aminotransferase and glutamate dehydrogenase in nitrogen metabolism in Mycobacterium bovis BCG.

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    Albertus J Viljoen

    Full Text Available Recent evidence suggests that the regulation of intracellular glutamate levels could play an important role in the ability of pathogenic slow-growing mycobacteria to grow in vivo. However, little is known about the in vitro requirement for the enzymes which catalyse glutamate production and degradation in the slow-growing mycobacteria, namely; glutamine oxoglutarate aminotransferase (GOGAT and glutamate dehydrogenase (GDH, respectively. We report that allelic replacement of the Mycobacterium bovis BCG gltBD-operon encoding for the large (gltB and small (gltD subunits of GOGAT with a hygromycin resistance cassette resulted in glutamate auxotrophy and that deletion of the GDH encoding-gene (gdh led to a marked growth deficiency in the presence of L-glutamate as a sole nitrogen source as well as reduction in growth when cultured in an excess of L-asparagine.

  3. Local skin reaction following an accidental injection from a BCG vaccine in a healthcare worker

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    Kundan Mittal

    2011-02-01

    Full Text Available Exposure to blood-borne pathogens from sharp injuriescontinue to pose a significant risk to healthcare workers(HCW. The number of sharps injuries sustained by HCW is stillunclear, primarily due to under-reporting of events.Healthcare professionals are at risk of sustaining such injuriesfrom hollow-bore needles. Sharps injuries are associated withrisk of infection with blood-borne pathogens such as humanimmunodeficiency virus (HIV, hepatitis B virus (HBV hepatitisC virus (HCV and other live organisms. Here we are reportinga case of an adverse reaction in a HCW due to an accidentalsharps injury by a needle used to administer the BacillusCalmittee Gurien (BCG vaccine.

  4. EFISIENSI PERSAINGAN BANK UMUM SYARIAH: PENDEKATAN DATA ENVELOPMENT ANALYSIS (DEA DAN BOSTON CONSULTING GROUP (BCG

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    Rizqon Halal Syah Aji

    2015-10-01

    Full Text Available Islamic Banking industry in Indonesia has begun dynamic. Product availability and standardization of Islamic banking products, the level of understanding by the public of products of Islamic banks and human resources. Market share of Islamic Banking in Indonesia to lock everything. Recent data Directorate of Islamic Banking in 2011 reached Rp 127,19 T, assets of BPRS amounting to Rp 3.35 T, can be calculated total Islamic banking assets as of October 2011 reached Rp 130,5 T. Financing very important factor, Data Envelopment Analisys (DEA is a measuring instrument of financing. Map of the Bank's performance in the competition between banks can be analyzed by matrix BCG (Boston Consulting Group. This matrix is used to describe the difference between the position of the relative market share of the Bank.DOI: 10.15408/sjie.v3i1.2059

  5. BCG-vaccination of newborns – a descriptive study about shared decision making and decisional conflicts

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte

    mothers, 662 (67 %) had a score single parent status. To investigate the extent to which the decisional conflicts reflected inadequate knowledge......BCG-vaccination of newborns – a descriptive study about shared decision making and decisional conflicts Objective: To evaluate the use of shared decision making to support the parent in a low-evidence decision about a vaccine when using telephone consultations. The present study was conducted.......9 % of the mothers felt that they had inadequate support. Almost half of the mothers (43.7 %) were uncertain about the best choice, indicating that they were not confident that they had made the right decision. Discussion: Because all parents received both written information and were offered personal counselling...

  6. Production of BCG alginate-PLL microcapsules by emulsification/internal gelation.

    Science.gov (United States)

    Esquisabel, A; Hernández, R M; Igartua, M; Gascón, A R; Calvo, B; Pedraz, J L

    1997-01-01

    A biocompatible emulsification method for microencapsulation of live cells and enzymes within a calcium alginate matrix applied to Bacillus Calmette-Guérin (BCG) has been developed. Small-diameter alginate beads (microcapsules) were formed via internal gelation of an alginate solution emulsified within vegetable oil. Five different oils (sesame, sweet almond, perhydrosqualene, camomile and jojoba) were used. The rheological analysis of the oils showed a Newtonian behaviour, with viscosities = 30.0, 37.7, 51.2, 59.3 and 67.1 mPa.s for perhydrosqualene, jojoba, camomile, sesame and sweet almond oil respectively. The particle size of the microcapsules obtained ranged from 30.3 microns for the microcapsules prepared with sweet almond oil to 57.0 microns for those made with perhydrosqualene. The mean particle diameter obtained was found to be dependent on the viscosity of the oil employed, according to the equation: phi (micron) = 76.6-0.628 eta (mPa.s) (r2 = 0.943). The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Freeze-drying of the microcapsules was carried out to ensure their stability during storage. Two batches of microcapsules (those prepared with sesame and jojoba oil) and four types of cryoprotectors (glucose, trehalose, mannitol and sorbitol), at three concentration levels (5, 10 and 20% w/v) were studied. The parameters evaluated were particle size, physical appearance, reconstitution of lyophilizates and microscopical evaluation. For both batches of microcapsules the best results were obtained with trehalose 5%, showing particle sizes of 42.1 microns in the case of the microcapsules prepared with sesame oil, and of 45.3 microns for those prepared with jojoba.

  7. Combined immunochemotherapy (CEP, M-VEP + BCG) in the treatment of invasive bladder tumors.

    Science.gov (United States)

    Damianov, C; Terziev, T; Koleva, P; Chuchkova, M

    1994-06-01

    Forty patients with invasive bladder tumors were consecutively treated and followed between June 1986 and February 1993. The treatment included systemic chemotherapy combining cyclophosphamide, epirubicin and cisplatin (CEP) or methotrexate, vinblastine, epirubicin and cisplatin (M-VEP) along with intravesically applied BCG vaccine. The treatment was well tolerated by the patients. No relevant toxic effects requiring hospitalization or fatalities due to the treatment were observed. Toxic manifestations of a hematologic nature were considerably less frequent than usual, nausea and vomiting being among the most frequently observed toxic signs on the second day of application of cisplatin. The side effects resulting from intravesically applied BCG vaccine showed no significant difference in terms of severity and variety from those due to its application in superficial tumors. A median follow-up of 50.3 months (range 6-80 months) showed an objective response to the treatment as follows: complete and partial response in 27 out of 40 (67.5%) and a complete clinical response in eight out of 40 (20%). Ten patients with partial response and stabilization had complete surgical response after operative treatment. The recurrence rate in patients with a complete response and a complete surgical response was 33% (six out of 18). The survival rate was 78% at 1 year, 70% at 2 years and 68% at 4 years. A complete response to the treatment of concomitant carcinoma in situ was observed in three patients. The lack of comparative and randomized studies and insufficient clinical experience did not allow an overall assessment of the therapeutic opportunities that our combined immunochemotherapy offers.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. An Analytical Delay Model

    Institute of Scientific and Technical Information of China (English)

    MIN Yinghua; LI Zhongcheng

    1999-01-01

    Delay consideration has been a majorissue in design and test of high performance digital circuits. Theassumption of input signal change occurring only when all internal nodesare stable restricts the increase of clock frequency. It is no longertrue for wave pipelining circuits. However, previous logical delaymodels are based on the assumption. In addition, the stable time of arobust delay test generally depends on the longest sensitizable pathdelay. Thus, a new delay model is desirable. This paper explores thenecessity first. Then, Boolean process to analytically describe thelogical and timing behavior of a digital circuit is reviewed. Theconcept of sensitization is redefined precisely in this paper. Based onthe new concept of sensitization, an analytical delay model isintroduced. As a result, many untestable delay faults under thelogical delay model can be tested if the output waveforms can be sampledat more time points. The longest sensitizable path length is computedfor circuit design and delay test.

  9. The current state of introduction of human papillomavirus vaccination into national immunisation schedules in Europe: first results of the VENICE2 2010 survey.

    Science.gov (United States)

    Dorleans, F; Giambi, C; Dematte, L; Cotter, S; Stefanoff, P; Mereckiene, J; O'Flanagan, D; Lopalco, P L; D'Ancona, F; Levy-Bruhl, D

    2010-11-25

    The Venice 2 human papillomavirus vaccination survey evaluates the state of introduction of the HPV vaccination into the national immunisation schedules in the 29 participating countries. As of July 2010, 18 countries have integrated this vaccination. The vaccination policy and achievements vary among those countries regarding target age groups, delivery infrastructures and vaccination coverage reached. Financial constraints remain the major obstacle for the 11 countries who have not yet introduced the vaccination.

  10. BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro

    DEFF Research Database (Denmark)

    Madura Larsen, Jeppe; Benn, Christine Stabell; Fillie, Yvonne;

    2007-01-01

    enhanced IL-10 and diminished IL-12 production. These DCs primed naive T cells to develop into IL-10-producing T cells, with no T helper 1 or T helper 2 bias. These results suggest that BCG vaccination might result in the development of IL-10-producing DCs as well as IL-10-producing T cells that could......Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine has been associated with beneficial effects on overall childhood mortality in low-income countries; this cannot be explained merely by the prevention of tuberculosis (TB) deaths. The beneficial effects of BCG vaccine could be the result...... of either strengthening of pro-inflammatory mechanisms, helping neonates to fight infections, or the induction of an immune-regulatory network restricting overt inflammation and intense pathology. We aimed to study the effect of live BCG on the ability of dendritic cells (DCs) to polarize T-cell responses...

  11. Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants.

    Directory of Open Access Journals (Sweden)

    April Kaur Randhawa

    2011-08-01

    Full Text Available The development of effective immunoprophylaxis against tuberculosis (TB remains a global priority, but is hampered by a partially protective Bacillus Calmette-Guérin (BCG vaccine and an incomplete understanding of the mechanisms of immunity to Mycobacterium tuberculosis. Although host genetic factors may be a primary reason for BCG's variable and inadequate efficacy, this possibility has not been intensively examined. We hypothesized that Toll-like receptor (TLR variation is associated with altered in vivo immune responses to BCG. We examined whether functionally defined TLR pathway polymorphisms were associated with T cell cytokine responses in whole blood stimulated ex vivo with BCG 10 weeks after newborn BCG vaccination of South African infants. In the primary analysis, polymorphism TLR6_C745T (P249S was associated with increased BCG-induced IFN-γ in both discovery (n = 240 and validation (n = 240 cohorts. In secondary analyses of the combined cohort, TLR1_T1805G (I602S and TLR6_G1083C (synonymous were associated with increased IFN-γ, TLR6_G1083C and TLR6_C745T were associated with increased IL-2, and TLR1_A1188T was associated with increased IFN-γ and IL-2. For each of these polymorphisms, the hypo-responsive allele, as defined by innate immunity signaling assays, was associated with increased production of TH1-type T cell cytokines (IFN-γ or IL-2. After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes. In contrast, no IL-12p70 was secreted by PBMCs or monocytes. These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12. These studies provide evidence that functionally defined innate immune gene variants are associated with the

  12. The introduction of the meningococcal B (MenB) vaccine (Bexsero®) into the national infant immunisation programme--New challenges for public health.

    Science.gov (United States)

    Ladhani, Shamez N; Campbell, Helen; Parikh, Sydel R; Saliba, Vanessa; Borrow, Ray; Ramsay, Mary

    2015-12-01

    The United Kingdom is the first country to introduce Bexsero(®) (GSK Biologicals), a multicomponent, protein-based vaccine against meningococcal group B (MenB), into the national infant immunisation programme. This vaccine is like no other licensed vaccine and poses a number of implementation and surveillance challenges in England. From 01 September 2015, UK infants were offered a reduced two dose primary immunisation schedule at 2 and 4 months followed by a booster at 12 months. Because of high rates of fever post-vaccination, parents were advised to give their infants three doses of prophylactic paracetamol, with the first dose given as soon as possible after the primary MenB vaccination dose. Since the vaccine only protects against 73-88% of MenB strains causing invasive disease in England, clinical isolates and PCR-positive samples will require extensive characterisation by the Meningococcal Reference Unit (MRU) at Public Health England (PHE) in order to monitor vaccine effectiveness and identify potential vaccine failures. PHE is also conducting detailed clinical and epidemiological surveillance to assess the impact of the MenB immunisation programme on the morbidity and mortality associated with invasive meningococcal disease in infants and young children.

  13. Influence of levamisole and Freund's adjuvant on mouse immunisation with antigens of adults of the liver fluke Fasciola hepatica Linnaeus, 1758.

    Science.gov (United States)

    Gutierrez-Sanchez, Maria de Los Angeles; Luna-Herrera, Julieta; Trejo-Castro, Lauro; Montenegro-Cristino, Natividad; Almanza-Gonzalez, Alfredo; Escobar-Gutierrez, Alejandro; de la Rosa-Arana, Jorge Luis

    2015-08-28

    We have studied the influence of both levamisole (AL) and Freund's adjuvant (AF) on the immunisation of mice with the secretory antigens of adults of the liver fluke Fasciola hepatica Linnaeus, 1758. Total IgG antibodies were detected in all groups where the F. hepatica antigen was administered, been levels of IgG1 increased respect to IgG2a antibodies. During immunisation, IL-4 and IFN-γ were only detected in AL and AF groups, but after infection, IL-4 boosted in all groups. IFN-γ increased two fold in AF and AL groups compared to the saline solution (AS) group. Worm recovering was of 32-35% in groups administered without antigen whereas in AS, AL and AF groups recovering was of 25%, 12% and 8%, respectively. Macroscopical lesions in the liver were scarce in AL and AF groups. Our data suggest that immunisation of mice with antigens of F. hepatica enhances the immune response avoiding both liver damage and worm establishment after challenge infection. The murine model of fasciolosis has appeared to be useful to elucidate the mechanism by which the parasite modulates immune responses toward a Th2 type but also the development of Th1 type-inducing vaccines.

  14. Effects of Ganoderma sterols (GS) on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    XinWANG; DanLI; Guo-liangZHANG; Zhi-binLIN

    2004-01-01

    AIM: To investigate effects of Ganoderma sterols (GS) isolated from Ganoderma lucidum (Leyss ex fr) Karst on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice and its possible mechanism. METHODS: Immunological liver injury was induced by one intravenous injection of BCG (125 mg/kg) in BALB/c mice. One week later, successiveintragastric administration of GS (20, 40, 80 mg/kg, per day) and

  15. The tuberculin skin test (TST is affected by recent BCG vaccination but not by exposure to non-tuberculosis mycobacteria (NTM during early life.

    Directory of Open Access Journals (Sweden)

    Sarah Burl

    Full Text Available The tuberculin skin test (TST is widely used in TB clinics to aid Mycobacterium tuberculosis (M.tb diagnosis, but the definition and the significance of a positive test in very young children is still unclear. This study compared the TST in Gambian children at 4(1/2 months of age who either received BCG vaccination at birth (Group 1 or were BCG naïve (Group 2 in order to examine the role of BCG vaccination and/or exposure to environmental mycobacteria in TST reactivity at this age. Nearly half of the BCG vaccinated children had a positive TST (>or=5 mm whereas all the BCG naïve children were non-reactive, confirming that recent BCG vaccination affects TST reactivity. The BCG naïve children demonstrated in vitro PPD responses in peripheral blood in the absence of TST reactivity, supporting exposure to and priming by environmental mycobacterial antigens. Group 2 were then vaccinated at 4(1/2 months of age and a repeat TST was performed at 20-28 months of age. Positive reactivity (>or=5 mm was evident in 11.1% and 12.5% infants from Group 1 and Group 2 respectively suggesting that the timing of BCG vaccination had little effect by this age. We further assessed for immune correlates in peripheral blood at 4(1/2 months of age. Mycobacterial specific IFNgamma responses were greater in TST responders than in non-responders, although the size of induration did not correlate with IFNgamma. However the IFNgamma: IL-10 ratio positively correlated with TST induration suggesting that the relationship between PPD induced IFNgamma and IL-10 in the peripheral blood may be important in controlling TST reactivity. Collectively these data provide further insights into how the TST is regulated in early life, and how a positive response might be interpreted.

  16. T-Cell mRNA Expression in Response to Mycobacterium bovis BCG Vaccination and Mycobacterium bovis Infection of White-Tailed Deer▿

    OpenAIRE

    Tyler C Thacker; Palmer, Mitchell V.; Waters, W. Ray

    2009-01-01

    Understanding immune responses of white-tailed deer (WTD) to infection with Mycobacterium bovis provides insight into mechanisms of pathogen control and may provide clues to development of effective vaccine strategies. WTD were vaccinated with either M. bovis BCG strain Pasteur or BCG strain Danish. Both vaccinees and unvaccinated controls were subsequently inoculated with virulent M. bovis via the intratonsillar route. Real-time PCR was used to assess T-cell mRNA expression in peripheral blo...

  17. Valor preditivo do teste tuberculínico padronizado em crianças vacinadas com BCG The predictive value of the standard tuberculin test in BCG-vaccinated children

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1992-08-01

    Full Text Available A aplicabilidade do teste tuberculínico em crianças menores de 5 anos vacinadas com BCG é assunto controvertido. Visando contribuir para esclarecê-lo foi analisado o valor preditivo positivo do teste tuberculínico padronizado em população sob elevada cobertura vacinal e baixa prevalência de infecção tuberculosa. A partir da proporção de reatores fortes em lactentes e escolares vacinados e não vacinados, foram calculadas a razão de declínio da alergia tuberculínica nos vacinados e a razão de crescimento nos não vacinados, o que possibilitou a estimativa dos respectivos valores nas idades intermediárias. A expectativa de falsos-positivos (FP foi então calculada por diferença. Conhecidas a sensibilidade e a especificidade do teste (E=1-FP, a cobertura BCG e a prevalência de infecção, os valores preditivos (para a infecção tuberculosa foram: 1,52%, 4,22%, 8,26%, 14,86% e 23,00%, do primeiro ao quinto ano de vida. Nessas condições, a probabilidade de uma reação forte ser devida ao BCG é grande, especialmente nos dois primeiros anos, o que reduz a aplicabilidade clínica e epidemiológica do teste.The applicability of tuberculin test in children under five years of age, BCG-vaccinated during their first year of life, is a controversial matter. With a view to clarifying the subject the predictive positive value of the test in a region of high BCG coverage and low prevalence of tuberculous infection was analysed. From the proportion of strong reactors among infants and school-age children, vaccinated and not unvaccinated, the declining rate of BCG induced allergy and the increment rate of naturally acquired tuberculin sensitivity between the first and the seventh years of life were calculated. Those calculations allowed for the estimation of the respective values for the intermediate ages. The numbers of false positives to be expected were calculated by difference. Knowing the sensibility and the especificity (1 - FP of

  18. La Matriz BCG (Boston Consulting Group para la Gestión de Publicaciones Periádicas The BCG (Boston Consulting Group matrix for management of periodic publications

    Directory of Open Access Journals (Sweden)

    Mª del Pilar Serrano Gallardo

    2005-11-01

    Full Text Available El marketing documental se ha de encargar de satisfacer las necesidades informativas de los usuarios de forma rentable para ellos y para el centro; para ello se ha de partir de un conjunto de herramientas técnicas que se conocen como el Marketing - Mix, y que abarcan el Producto, el Precio, la Distribución y la Comunicación. Dentro de las herramientas destinadas al producto se encuentra la matriz BCG (Boston Consulting Group, que está orientada a gestión, sobre la base de la situación del producto en el mercado. El objetivo del presente artículo es proponer una matriz BCG para la gestión de una publicación periódica enfermera en nuestro mercado.La matriz BCG se construye con dos variables: el Crecimiento del Mercado y la Tasa Relativa del Mercado, las cuales se han operacionalizado como Media de Crecimiento Anual en el número de suscripciones de tres revistas enfermeras (Rol de Enfermería, Metas de Enfermería y Nursing durante el último quinquenio y Media de Tirada Actual de las tres publicaciones. Se han utilizado datos ofrecidos por la Oficina para el Control de la Difusión (OJD. La matriz BCG puede constituirse como herramienta básica en la gestión de publicaciones, dado que tras determinar la situación del producto, se pueden establecer estrategias que ayuden o favorezcan el mejor posicionamiento posible del producto en el mercado.Documentary marketing has to address the information needs of the users in a manner that is cost-effective not only for them but also for the institution. To do this, a set of technical tools, known as Marketing- Mix, need to be used. These tools include the Product, Price, Distribution and Communication. Within the set of tools used for the Product, we find the BCG matrix (Boston Consulting Group, a tool aimed at the management of the product on the basis of where it is positioned in the market. The objective of this paper is to propose a BCG matrix for the management of a nursing periodic

  19. Identification of Botrytis cinerea genes up-regulated during infection and controlled by the Galpha subunit BCG1 using suppression subtractive hybridization (SSH).

    Science.gov (United States)

    Schulze Gronover, Christian; Schorn, Corinna; Tudzynski, Bettina

    2004-05-01

    The Galpha subunit BCG1 plays an important role during the infection of host plants by Botrytis cinerea. Delta bcg1 mutants are able to conidiate, penetrate host leaves, and produce small primary lesions. However, in contrast to the wild type, the mutants completely stop invasion of plant tissue at this stage; secondary lesions have never been observed. Suppression subtractive hybridization (SSH) was used to identify fungal genes whose expression on the host plant is specifically affected in bcg1 mutants. Among the 22 differentially expressed genes, we found those which were predicted to encode proteases, enzymes involved in secondary metabolism, and others encoding cell wall-degrading enzymes. All these genes are highly expressed during infection in the wild type but not in the mutant. However, the genes are expressed in both the wild type and the mutant under certain conditions in vitro. Most of the BCG1-controlled genes are still expressed in adenylate cyclase (bac) mutants in planta, suggesting that BCG1 is involved in at least one additional signaling cascade in addition to the cAMP-depending pathway. In a second SSH approach, 1,500 clones were screened for those that are specifically induced by the wild type during the infection of bean leaves. Of the 22 BCG1-controlled genes, 11 also were found in the in planta SSH library. Therefore, SSH technology can be successfully applied to identify target genes of signaling pathways and differentially expressed genes in planta.

  20. Construction and Expression of the Echinococcus granulosus Recombinant BCG-EgG1Y162%细粒棘球绦虫重组BCG-EgG1Y162菌株的构建和表达

    Institute of Scientific and Technical Information of China (English)

    祖力皮也·吐尔逊; 德力夏提·依米提; 曹春宝; 马海梅; 李玉娇; 周晓涛; 朱明; 马秀敏; 温浩

    2013-01-01

    Objective To construct and express Echinococcus granulosus recombinant bacille Calmette-Guerin (BCG) strain rBCG-EgG1Y162. Methods The encoding gene of the antigen EgG1Y162 of E. granulosus was recombined with E. coli-Mycobacterium shuttle expression plasmid vector pMV361 by genetic engineering technique, and transformed into E. coll for amplification. The recombinant plasmid rpMV-EgG1Y162 was identified by PCR, double digestion with restriction enzymes, and sequence analysis. The confirmed rpMV-EgG1Y162 was transformed into BCG strain via electroporation technique to construct the recombinant rBCG-EgG1Y162. After identification by PCR and double digestion with restriction enzymes, the recombinant strain was cultured for about 2 weeks. In order to induce the expression of target protein, the rBCG was placed in 45℃ for 30 min. SDS-PAGE and Western blotting were used to analyze the expressive protein. Results The product of recombinant plasmid rpMV-EgG1Y162 was approximately 360 bp by PCR amplification and double digestion with restriction enzymes, consistent with the expected fragment length. Sequencing results showed that the inserted sequence was correct. The rBCG-EgG1Y162 grew well and the identification of PCR and enzyme digestion revealed accuracy. The results of SDS-PAGE and Western blotting showed that the relative molecular weight (Mr) of the protein was about 71 000. Conclusion The E. granulosus rBCG-EgG1Y162 strain is constructed and expressed.%目的 构建和表达细粒棘球绦虫重组卡介苗(BCG)菌株rBCG-EgG1Y162.方法 通过基因工程技术将细粒棘球绦虫抗原EgG1Y162的编码基因与大肠埃希菌(E.coli)-分枝杆菌穿梭表达质粒载体pMV361重组,并转化E.coli后进行扩增.重组质粒pMV-EgG1Y162经PCR和双酶切鉴定后,进行测序.将鉴定正确的rpMV-EgG1Y162通过电穿孔技术转化至感受态BCG菌株中,构建rBCG-EgG1Y162.经PCR和双酶切鉴定正确后,扩增培养2周,并于45℃放置30 min,诱导

  1. Delayed emergence after anesthesia.

    Science.gov (United States)

    Tzabazis, Alexander; Miller, Christopher; Dobrow, Marc F; Zheng, Karl; Brock-Utne, John G

    2015-06-01

    In most instances, delayed emergence from anesthesia is attributed to residual anesthetic or analgesic medications. However, delayed emergence can be secondary to unusual causes and present diagnostic dilemmas. Data from clinical studies is scarce and most available published material is comprised of case reports. In this review, we summarize and discuss less common and difficult to diagnose reasons for delayed emergence and present cases from our own experience or reference published case reports/case series. The goal is to draw attention to less common reasons for delayed emergence, identify patient populations that are potentially at risk and to help anesthesiologists identifying a possible cause why their patient is slow to wake up.

  2. Altered Liver Proteoglycan/Glycosaminoglycan Structure as a Manifestation of Extracellular Matrix Remodeling upon BCG-induced Granulomatosis in Mice.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2017-01-01

    Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

  3. An oral Mycobacterium bovis BCG vaccine for wildlife produced in the absence of animal-derived reagents.

    Science.gov (United States)

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2009-09-01

    Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products.

  4. [Ag85B and BCG enhance immune activity of dendritic cells in patients with initially treated tuberculosis].

    Science.gov (United States)

    Guo, Yun; Su, Yuanyuan; Sun, Yang; Guan, Weiwei; Yang, Li; Zhang, Zhi; Wang, Yuling; Dai, Erhei

    2016-06-01

    Objective To investigate the regulatory effects of Mycobacterium tuberculosis major secreted protein Ag85B and Bacillus Calmette-Guerin (BCG) on the immune function of dendritic cells (DCs) in the patients with tuberculosis who have received an initial treatment. Methods The peripheral blood mononuclear cells were collected and separated in 26 healthy subjects and 31 patients with tuberculosis who had been treated initially. Every specimen was divided into 4 groups and DCs were induced and cultured. On the 6th day, the DCs in the three experimental groups were treated by lipopolysaccharide (LPS), BCG, Ag85B, respectively and no-treated DCs served as a control group. After 24-hour treatment, DCs were collected and examined for the levels of CD83, CD86, HLA-DR and CD11c using flow cytometry. Moreover, the levels of interleukin 12 (IL-12), IL-10 and interferon γ (IFN-γ) in the supernatants were measured by ELISA. Results The expression levels of CD83 and IL-10 in the patient control group were significantly lower than those in healthy subject control group. The levels of CD83, CD86 and IFN-γ in the Ag85B treated group were obviously high than those in the control group. The level of IFN-γ in the BCG treated group was significantly high than that in the control group. The levels of CD83, CD86, HLA-DR and IL-10 in the LPS treated group were remarkably higher than those in the control group. The levels of CD83, CD86 and IL-10 in the healthy subject LPS treated group were significantly higher than those in the healthy subject control group. Conclusion The immune-enhancing effect of Ag85B on DCs is superior to that of BCG in the patients with initially treated tuberculosis.

  5. The role of the mycobacterial DNA-binding protein 1 (MDP1 from Mycobacterium bovis BCG in host cell interaction

    Directory of Open Access Journals (Sweden)

    Kunisch Ralph

    2012-08-01

    Full Text Available Abstract Background Mycobacterium tuberculosis differs from most pathogens in its ability to multiply inside monocytes and to persist during long periods of time within granuloma in a status of latency. A class of proteins called mycobacterial histone-like proteins has been associated with regulation of replication and latency, but their precise role in the infection process has yet to be uncovered. Our study aimed at defining the impact of the histone-like protein MDP1 from M. bovis BCG (mycobacterial DNA-binding protein 1, corresponding to Rv2986c from M. tuberculosis on early steps of infection. Results Previously, a BCG (Bacillus Calmette Guérin strain had been generated by antisense-technique exhibiting reduced MDP1 expression. This strain was now used to analyse the impact of reduced amount of MDP1 on the interaction with human blood monocytes, macrophage lines and PBMC (peripheral blood mononuclear cells. MDP1 was revealed to be required for growth at acidic pH and for intracellular replication in human blood monocytes. Down-regulation of MDP1 resulted in reduced secretion of the cytokine IL-1β by infected human PBMC. In addition, a reduction of MDP1 expression had a major impact on the formation of fused multi-nucleated macrophages. In monocyte preparations from human blood as well as in human and mouse macrophage cell lines, both the percentage of multi-nucleated cells and the number of nuclei per cell were much enhanced when the monocytes were infected with BCG expressing less MDP1. Conclusion MDP1 from M. bovis BCG affects the growth at acidic pH and the intracellular replication in human monocytes. It furthermore affects cytokine secretion by host cells, and the formation of fused multi-nucleated macrophages. Our results suggest an important role of MDP1 in persistent infection.

  6. The toxicity of rifampicin polylactic acid nanoparticles against Mycobacterium bovis BCG and human macrophage THP-1 cell line

    Science.gov (United States)

    Erokhina, M.; Rybalkina, E.; Barsegyan, G.; Onishchenko, G.; Lepekha, L.

    2015-11-01

    Tuberculosis is rapidly becoming a major health problem. The rise in tuberculosis incidence stimulates efforts to develop more effective delivery systems for the existing antituberculous drugs while decreasing the side effects. The nanotechnology may provide novel drug delivery tools allowing controlled drug release. Rifampicin is one of the main antituberculous drugs, characterized by high toxicity, and Poly (L-lactic acid) (PLLA) is a biodegradable polymer used for the preparation of encapsulated drugs. The aim of our work was to evaluate the toxicity of rifampicin-PLLA nanoparticles against Mycobacterium bovis BCG using human macrophage THP-1 cell line. Our data demonstrate that rifampicin-PLLA is effective against M. bovis BCG in the infected macrophages. The drug is inducing the dysfunction of mitochondria and apoptosis in the macrophages and is acting as a potential substrate of Pgp thereby modulating cell chemosensitivity. The severity of the toxic effects of the rifampicin-PLLA nanoparticles is increasing in a dose-dependent manner. We suggest that free rifampicin induces death of M. bovis BCG after PLLA degradation and diffusion from phago-lysosomes to cytoplasm causing mitochondria dysfunction and affecting the Pgp activity.

  7. Diseases masking and delaying the diagnosis of urogenital tuberculosis.

    Science.gov (United States)

    Kulchavenya, Ekaterina; Kholtobin, Denis

    2015-12-01

    As urogenital tuberculosis (UGTB) has no specific clinical features, it is often overlooked. To identify some of the reasons for misdiagnosing UGTB we performed a systematic review. We searched in Medline/PubMed papers with keywords 'urogenital tuberculosis, rare' and 'urogenital tuberculosis, unusual'. 'Urogenital tuberculosis, rare' presented 230 articles and 'urogenital tuberculosis, unusual' presented 81 articles only, a total of 311 papers. A total of 34 papers were duplicated and so were excluded from the review. In addition, we excluded from the analysis 33 papers on epidemiological studies and literature reviews, papers describing non-TB cases and cases of TB another than urogenital organs (48 articles), cases of congenital TB (three articles), UGTB as a case of concomitant disease (16 articles), and UGTB as a complication of BCG-therapy (eight articles). We also excluded 22 articles dedicated to complications of the therapy, which made a total of 164 articles. Among the remaining 147 articles we selected 43 which described really unusual, difficult to diagnose cases. We also included in our review a WHO report from 2014, and one scientific monograph on TB urology. The most frequent reasons for delayed diagnosis were absence typical clinical features of UGTB, and the tendency of UGTB to hide behind the mask of another disease. We can conclude that actually UGTB is not rare disease, but it is often an overlooked disease. The main reasons for delayed diagnosis are vague, atypical clinical features and a low index of suspicion.

  8. The Journalists Initiatives on Immunisation Against Polio and Improved Acceptance of the Polio Vaccine in Northern Nigeria 2007–2015

    Science.gov (United States)

    Warigon, Charity; Mkanda, Pascal; Banda, Richard; Zakari, Furera; Damisa, Eunice; Idowu, Audu; Bawa, Samuel; Gali, Emmanuel; Tegegne, Sisay G.; Hammanyero, Kulchumi; Nsubuga, Peter; Korir, Charles; Vaz, Rui G.

    2016-01-01

    Background. The polio eradication initiative had major setbacks in 2003 and 2007 due to media campaigns in which renowned scholars and Islamic clerics criticized polio vaccines. The World Health Organization (WHO) partnered with journalists in 2007 to form the Journalists Initiatives on Immunisation Against Polio (JAP), to develop communication initiatives aimed at highlighting polio eradication activities and the importance of immunization in northern Nigeria. Methods. We evaluated the impact of JAP activities in Kaduna State by determining the total number of media materials produced and the number of newspaper clips and bulletins published in support of polio eradication. We also determined the number of households in noncompliant communities that became compliant with vaccination during 2015 supplementary immunization activities (SIAs) after JAP interventions and compared caregivers’ sources of information about SIAs in 2007 before and after the JAP was formed. Results. Since creation of the JAP, >500 reports have been published and aired, with most portraying polio vaccine positively. During June 2015 SIAs in high-risk wards of Kaduna STATE, JAP interventions resulted in vaccination of 5122 of 5991 children (85.5%) from noncompliant households. During early 2007, the number of caregivers who had heard about SIA rounds from the media increased from 26% in January, before the JAP was formed, to 33% in March, after the initiation of JAP activities. Conclusions. The formation of the JAP resulted in measurable improvement in the acceptance of polio vaccine in northern Nigeria. PMID:26721745

  9. Reducing resistance to polio immunisation with free health camps and Bluetooth messaging: An update from Kaduna, Northern, Nigeria.

    Science.gov (United States)

    Birukila, Gerida; Babale, Sufiyan M; Epstein, Helen; Gugong, Victor; Anger, Robert; Corkum, Melissa; Jehoshaphat Nebanat, Albarka; Musoke, Fredrick; Alabi, Olaniran

    2017-01-01

    Since 1997, the Global Polio Eradication Initiative has sponsored regular door-to-door polio immunisation campaigns in northern Nigeria. On 30 July 2015, the country was finally declared poliofree, a hard won success. At various times, polio eradication has been threatened by rumours and community tensions. For example, in 2003, local Imams, traditional leaders and politicians declared a polio campaign boycott, due to the concerns about the safety of the polio vaccine. Although the campaigns resumed in 2004, many parents continued to refuse vaccination because of the persistence of rumours of vaccine contamination, and anger about the poor state of health services for conditions other than polio. To address this, UNICEF and Nigerian Government partners piloted two interventions: (1) mobile 'health camps' to provide ambulatory care for conditions other than polio and (2) an audiovisual clip about vaccine safety and other health issues, shareable on multimedia mobile phones via Bluetooth pairing. The mobile phone survey found that Bluetooth compatible messages could rapidly spread behavioural health messages in low-literacy communities. The health camps roughly doubled polio vaccine uptake in the urban ward where it was piloted. This suggests that polio eradication would have been accelerated by improving primary health care services.

  10. 75 cases of BCG (BCG) after vaccination with abnormal response of curative effect observation and nursing%75例卡介苗(BCG)接种后异常反应的疗效观察及护理

    Institute of Scientific and Technical Information of China (English)

    秦曼玲

    2013-01-01

    Objective:Study of BCG after vaccination with abnormal response of curative effect observation and nursing. Methods:To BCG after inoculation of common abnormal reaction were summarized and analyzed and appropriate nursing measures. Results:BCG after vaccination abnormal reactions occurred in the left side of vaccination vaccine, it is the most in axil ary lymphadenopathy. Lymph nodes found in the after inoculation of 2-7month , it’s Most in 3-4month, Lymph node enlargement of diameter in 1~3 cm, Al were cured after comprehensive treatment, the cure rate is 100%. Conclusions:In BCG vaccination, we want to do good conduct propaganda and In order to reduce the abnormal reactions after inoculation of BCG vaccination, we should strengthen professional training and take treatment and nursing measures to abnormal response and ensure children Physical and mental health.%目的:探讨卡介苗(BCG)接种后异常反应的疗效观察及护理。方法:对卡介苗(BCG)接种后的常见异常反应进行总结分析,并采取适当的护理措施。结果:卡介苗(BCG)接种后异常反应均发生在左侧接种菌苗侧,以腋下淋巴结肿大为最多,淋巴结肿大发现于接种后2~7个月,大部分为3~4个月。淋巴结肿大直径以1~3 cm多见。经综合治疗后,全部治愈,治愈率达100%。结论:在进行卡介苗接种时,要做好宣传,为减少接种后异常反应的发生,应加强卡介苗接种人员的业务培训,发现异常反应要及时采取有效的治疗及护理措施,确保儿童的身心健康。

  11. Efficient activation of human T cells of both CD4 and CD8 subsets by urease-deficient recombinant Mycobacterium bovis BCG that produced a heat shock protein 70-M. tuberculosis-derived major membrane protein II fusion protein.

    Science.gov (United States)

    Mukai, Tetsu; Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Makino, Masahiko

    2014-01-01

    For the purpose of obtaining Mycobacterium bovis bacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed of Mycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8(+) T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8(+) T cells and perforin-producing effector CD8(+) T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive to in vitro secondary stimulation with HSP70, MMP-II, and M. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challenged M. tuberculosis more efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.

  12. First data on Eurasian wild boar response to oral immunization with BCG and challenge with a Mycobacterium bovis field strain.

    Science.gov (United States)

    Ballesteros, C; Garrido, J M; Vicente, J; Romero, B; Galindo, R C; Minguijón, E; Villar, M; Martín-Hernando, M P; Sevilla, I; Juste, R; Aranaz, A; de la Fuente, J; Gortázar, C

    2009-11-12

    The Eurasian wild boar (Sus scrofa) is considered a reservoir for bovine tuberculosis (bTB) caused by Mycobacterium bovis and closely related members of the Mycobacterium tuberculosis complex in south-central Spain. The vaccination of wildlife with BCG offers an alternative to culling and to movement restriction for the control of bTB among wildlife reservoirs. In this study, we hypothesized that oral BCG immunization of wild boar would affect the expression of immunoregulatory genes and confer protection against M. bovis. Three groups were used to describe the infection, pathological findings and gene expression profiles in wild boar: BCG-vaccinated and M. bovis-challenged (vaccinated challenged group; N=6), non-vaccinated and M. bovis-challenged (non-vaccinated challenged group; N=4), and non-vaccinated and mock-infected (control group; N=2) animals. M. bovis was isolated from 50% (3/6) and 75% (3/4) of vaccinated challenged and non-vaccinated challenged animals, respectively. All four wild boar from the non-vaccinated challenged group developed bTB-compatible lesions 114 days after challenge. In contrast, only 50% of vaccinated challenged wild boar developed lesions. The PBMC mRNA levels of IL4, RANTES, C3, IFN-gamma and methylmalonyl-CoA mutase (MUT) were analyzed at several days post-vaccination (dpi). When vaccinated challenged animals were compared to controls, all five genes were significantly upregulated at the time of M. bovis infection at 186dpi but IFN-gamma levels were also upregulated at 11 and 46dpi. The C3 and MUT mRNA levels were higher at 46dpi, and 11 and 186dpi, respectively, in vaccinated protected wild boar when compared to non-vaccinated challenged animals. At the end of the experiment (300dpi), the mRNA levels of selected genes were lower in non-vaccinated challenged animals when compared to control wild boar. Exposing wild boar to a dose of 10(4)cfu of M. bovis by the oropharyngeal route is an adequate protocol to produce an infection model

  13. Attrition of T-cell functions and simultaneous upregulation of inhibitory markers correspond with the waning of BCG-induced protection against tuberculosis in mice.

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    Subhadra Nandakumar

    Full Text Available Mycobacterium bovis bacille Calmette-Guérin (BCG is the most widely used live attenuated vaccine. However, the correlates of protection and waning of its immunity against tuberculosis is poorly understood. In this study, we correlated the longitudinal changes in the magnitude and functional quality of CD4(+ and CD8(+ T-cell response over a period of two years after mucosal or parenteral BCG vaccination with the strength of protection against Mycobacterium tuberculosis in mice. The BCG vaccination-induced CD4(+ and CD8(+ T cells exhibited comparable response kinetics but distinct functional attributes in-terms of IFN-γ, IL-2 and TNF-α co-production and CD62L memory marker expression. Despite a near life-long BCG persistence and the induction of enduring CD4(+ T-cell responses characterized by IFN-γ and/or TNF-α production with comparable protection, the protective efficacy waned regardless of the route of vaccination. The progressive decline in the multifactorial functional abilities of CD4(+ and CD8(+ T cells in-terms of type-1 cytokine production, proliferation and cytolytic potential corresponded with the waning of protection against M. tuberculosis infection. In addition, simultaneous increase in the dysfunctional and terminally-differentiated T cells expressing CTLA-4, KLRG-1 and IL-10 during the contraction phase of BCG-induced response coincided with the loss of protection. Our results question the empirical development of BCG-booster vaccines and emphasize the pursuit of strategies that maintain superior T-cell functional capacity. Furthermore, our results underscore the importance of understanding the comprehensive functional dynamics of antigen-specific T-cell responses in addition to cytokine polyfunctionality in BCG-vaccinated hosts while optimizing novel vaccination strategies against tuberculosis.

  14. Attrition of T-cell functions and simultaneous upregulation of inhibitory markers correspond with the waning of BCG-induced protection against tuberculosis in mice.

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Posey, James E; Amara, Rama Rao; Sable, Suraj B

    2014-01-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most widely used live attenuated vaccine. However, the correlates of protection and waning of its immunity against tuberculosis is poorly understood. In this study, we correlated the longitudinal changes in the magnitude and functional quality of CD4(+) and CD8(+) T-cell response over a period of two years after mucosal or parenteral BCG vaccination with the strength of protection against Mycobacterium tuberculosis in mice. The BCG vaccination-induced CD4(+) and CD8(+) T cells exhibited comparable response kinetics but distinct functional attributes in-terms of IFN-γ, IL-2 and TNF-α co-production and CD62L memory marker expression. Despite a near life-long BCG persistence and the induction of enduring CD4(+) T-cell responses characterized by IFN-γ and/or TNF-α production with comparable protection, the protective efficacy waned regardless of the route of vaccination. The progressive decline in the multifactorial functional abilities of CD4(+) and CD8(+) T cells in-terms of type-1 cytokine production, proliferation and cytolytic potential corresponded with the waning of protection against M. tuberculosis infection. In addition, simultaneous increase in the dysfunctional and terminally-differentiated T cells expressing CTLA-4, KLRG-1 and IL-10 during the contraction phase of BCG-induced response coincided with the loss of protection. Our results question the empirical development of BCG-booster vaccines and emphasize the pursuit of strategies that maintain superior T-cell functional capacity. Furthermore, our results underscore the importance of understanding the comprehensive functional dynamics of antigen-specific T-cell responses in addition to cytokine polyfunctionality in BCG-vaccinated hosts while optimizing novel vaccination strategies against tuberculosis.

  15. Improving Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer by adding interleukin 2 (IL-2): a mathematical model.

    Science.gov (United States)

    Bunimovich-Mendrazitsky, Svetlana; Halachmi, Sarel; Kronik, Natalie

    2016-06-01

    One of the treatments offered to non-invasive bladder cancer patients is BCG instillations, using a well-established, time-honoured protocol. Some of the patients, however, do not respond to this protocol. To examine possible changes in the protocol, we provide a platform for in silico testing of alternative protocols for BCG instillations and combinations with IL-2, to be used by urologists in planning new treatment strategies for subpopulations of bladder cancer patients who may benefit from a personalized protocol. We use a systems biology approach to describe the BCG-tumour-immune interplay and translate it into a set of mathematical differential equations. The variables of the equation set are the number of tumour cells, bacteria cells, immune cells, and cytokines participating in the tumour-immune response. Relevant parameters that describe the system's dynamics are taken from a variety of independent literature, unrelated to the clinical trial results assessed by the model predictions. Model simulations use a clinically relevant range of initial tumour sizes (tumour volume) and tumour growth rates (tumour grade), representative of a virtual population of fifty patients. Our model successfully retrieved previous clinical results for BCG induction treatment and BCG maintenance therapy with a complete response (CR) rate of 82%. Furthermore, we designed alternative maintenance protocols, using IL-2 combinations with BCG, which improved success rates up to 86% and 100% of the patients, albeit without considering possible side effects. We have shown our simulation platform to be reliable by demonstrating its ability to retrieve published clinical trial results. We used this platform to predict the outcome of treatment combinations. Our results suggest that the subpopulation of non-responsive patients may benefit from an intensified combined BCG IL-2 maintenance treatment.

  16. Immunomodulation of Homeopathic Thymulin 5CH in a BCG-Induced Granuloma Model

    Directory of Open Access Journals (Sweden)

    Leoni Villano Bonamin

    2013-01-01

    Full Text Available The present study analyzed the immune modulation mechanisms of thymulin 5CH in a granuloma experimental model. Male adult Balb/c mice were inoculated with BCG into the footpad to induce granuloma, which was quantitatively evaluated. The phenotypic characterization of phagocyte, T- and B-lymphocyte populations in the peritoneum, and local lymph node was done by flow cytometry. During all experimental periods, thymulin 5CH and vehicle (control were given ad libitum to mice, diluted into the drinking water (1.6×10−17 M. After 7 days from inoculation, thymulin-treated mice presented reduction in the number of epithelioid cytokeratine-positive cells (P=0.0001 in the lesion, in relation to young phagocytes. After 21 days, the differentiation of B1 peritoneal stem cells into phagocytes reached the peak, being higher in thymulin-treated mice (P=0.0001. Simultaneously, the score of infected phagocytes in the lesion decreased (P=0.001, and the number of B1-derived phagocytes, CD4+ and CD8+ T lymphocytes in the local lymph node increased in relation to control (P=0.0001. No difference was seen on the CD25+ Treg cells. The results show that thymulin 5CH treatment is able to improve the granuloma inflammatory process and the infection remission, by modulating local and systemic phagocyte differentiation.

  17. Contrary to BCG, MLM fails to induce the production of TNF alpha and NO by macrophages.

    Science.gov (United States)

    Rojas-Espinosa, Oscar; Wek-Rodríguez, Kendy; Arce-Paredes, Patricia; Aguilar-Torrentera, Fabiola; Truyens, Carine; Carlier, Yves

    2002-06-01

    Pathogenic mycobacteria must possess efficient survival mechanisms to resist the harsh conditions of the intraphagosomal milieu. In this sense, Mycobacterium lepraemurium (MLM) is one of the most evolved intracellular parasites of murine macrophages; this microorganism has developed a series of properties that allows it not only to resist, but also to multiply within the inhospitable environment of the phagolysosome. Inside the macrophages, MLM appears surrounded by a thick lipid-envelope that protects the microorganism from the digestive effect of the phagosomal hydrolases and the acid pH. MLM produces a disease in which the loss of specific cell-mediated immunity ensues, thus preventing activation of macrophages. In vitro, and possibly also in vivo, MLM infects macrophages without triggering the oxidative (respiratory burst) response of these cells, thus preventing the production of the toxic reactive oxygen intermediaries (ROI). Supporting the idea that MLM is within the most evolved pathogenic microorganisms, in the present study we found, that contrary to BCG, M. lepraemurium infects macrophages without stimulating these cells to produce meaningful levels of tumor necrosis factor alpha (TNF alpha) or nitric oxide (NO). Thus, the ability of the microorganisms to stimulate in their cellular hosts, the production of ROI and RNI (reactive nitrogen intermediates), seems to be an inverse correlate of their pathogenicity; the lesser their ability, the greater their pathogenicity.

  18. Variant RH alleles and Rh immunisation in patients with sickle cell disease

    Science.gov (United States)

    Sippert, Emilia; Fujita, Claudia R.; Machado, Debora; Guelsin, Glaucia; Gaspardi, Ane C.; Pellegrino, Jordão; Gilli, Simone; Saad, Sara S.T.O.; Castilho, Lilian

    2015-01-01

    Background Alloimmunisation is a major complication in patients with sickle cell disease (SCD) receiving red blood cell (RBC) transfusions and despite provision of Rh phenotyped RBC units, Rh antibodies still occur. These antibodies in patients positive for the corresponding Rh antigen are considered autoantibodies in many cases but variant RH alleles found in SCD patients can also contribute to Rh alloimmunisation. In this study, we characterised variant RH alleles in 31 SCD patients who made antibodies to Rh antigens despite antigen-positive status and evaluated the clinical significance of the antibodies produced. Materials and methods RHD and RHCE BeadChip™ from BioArray Solutions and/or amplification and sequencing of exons were used to identify the RH variants. The serological features of all Rh antibodies in antigen-positive patients were analysed and the clinical significance of the antibodies was evaluated by retrospective analysis of the haemoglobin (Hb) levels before and after transfusion; the change from baseline pre-transfusion Hb and the percentage of HbS were also determined. Results We identified variant RH alleles in 31/48 (65%) of SCD patients with Rh antibodies. Molecular analyses revealed the presence of partial RHD alleles and variant RHCE alleles associated with altered C and e antigens. Five patients were compound heterozygotes for RHD and RHCE variants. Retrospective analysis showed that 42% of antibodies produced by the patients with RH variants were involved in delayed haemolytic transfusion reactions or decreased survival of transfused RBC. Discussion In this study, we found that Rh antibodies in SCD patients with RH variants can be clinically significant and, therefore, matching patients based on RH variants should be considered. PMID:24960646

  19. commensurate point delays

    Directory of Open Access Journals (Sweden)

    M. de la Sen

    2005-01-01

    nominal controller is maintained. In the current approach, the finite spectrum assignment is only considered as a particular case of the designer's choice of a (delay-dependent arbitrary spectrum assignment objective.

  20. Time Delay Cosmography

    OpenAIRE

    Treu, Tommaso; Marshall, Philip J.

    2016-01-01

    Gravitational time delays, observed in strong lens systems where the variable background source is multiply-imaged by a massive galaxy in the foreground, provide direct measurements of cosmological distance that are very complementary to other cosmographic probes. The success of the technique depends on the availability and size of a suitable sample of lensed quasars or supernovae, precise measurements of the time delays, accurate modeling of the gravitational potential of the main deflector,...

  1. Enhancement of BCG-induced Th1 immune response through Vgamma9Vdelta2 T cell activation with non-peptidic drugs.

    Science.gov (United States)

    Martino, Angelo; Casetti, Rita; Poccia, Fabrizio

    2007-01-22

    Since drug-activated gammadelta T cells promote dendritic cell (DC) maturation, we analyzed the effect of combining gammadelta T cell specific drugs with BCG in vitro. BCG-induced DC maturation was increased by bromohydrin-pirophosphate (BrHPP) or zoledronate (Zol)-activated gammadelta T cells. Specifically, the co-culture with activated Vgamma9Vdelta2 T cells with BCG-infected DC resulted in a significant increase of the expression of CD80, CD86, CD40 and CD25 molecules on DC. Moreover, DC were able to produce increased levels of TNF-alpha and synthesize ex novo IL-15 without altering the IL-10/IL-12 immunoregulatory pathway. Finally, the Th1 immunity induced by BCG-infected DC on naïve CD4 T cells was increased by gammadelta T cell activation with BrHpp or Zol. These data indicate that gammadelta T cell triggering drugs could be used to enhance the BCG induced Th1 immunity.

  2. Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+CD56(bright cells.

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    Damien Portevin

    Full Text Available Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56(bright NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56(bright population. In summary, we observed that M. bovis BCG is modulating the functions of CD56(bright NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56(bright cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent.

  3. Detection of a Putative TetR-Like Gene Related to Mycobacterium bovis BCG Growth in Cholesterol Using a gfp-Transposon Mutagenesis System

    Science.gov (United States)

    Otal, Isabel; Pérez-Herrán, Esther; Garcia-Morales, Lazaro; Menéndez, María C.; Gonzalez-y-Merchand, Jorge A.; Martín, Carlos; García, María J.

    2017-01-01

    In vitro transposition is a powerful genetic tool for identifying mycobacterial virulence genes and studying virulence factors in relation to the host. Transposon shuttle mutagenesis is a method for constructing stable insertions in the genome of different microorganisms including mycobacteria. Using an IS1096 derivative, we have constructed the Tngfp, a transposon containing a promoterless green fluorescent protein (gfp) gene. This transposon was able to transpose randomly in Mycobacterium bovis BCG. Bacteria with a single copy of the gfp gene per chromosome from an M. bovis BCG::Tngfp library were analyzed and cells exhibiting high levels of fluorescence were detected by flow cytometry. Application of this approach allowed for the selection of a mutant, BCG_2177c::Tngfp (BCG-Tn), on the basis of high level of long-standing fluorescence at stationary phase. This BCG-Tn mutant showed some particular phenotypic features compared to the wild type strain, mainly during stationary phase, when cholesterol was used as a sole carbon source, thus supporting the relationships of the targeted gene with the regulation of cholesterol metabolism in this bacteria. This approach showed that Tngfp is a potentially useful tool for studying the involvement of the targeted loci in metabolic pathways of mycobacteria. PMID:28321208

  4. Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

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    JoĂŤl Pestel

    2008-06-01

    Full Text Available Mycobacterium bovis bacillus Calmette-GuĂŠrin (BCG is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

  5. Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated within a gel matrix: characterization of a new model of the granulomatous response to mycobacterial components.

    Science.gov (United States)

    Rhoades, Elizabeth R; Geisel, Rachel E; Butcher, Barbara A; McDonough, Sean; Russell, David G

    2005-05-01

    The chronic inflammatory response to Mycobacterium generates complex granulomatous lesions that balance containment with destruction of infected tissues. To study the contributing factors from host and pathogen, we developed a model wherein defined mycobacterial components and leukocytes are delivered in a gel, eliciting a localized response that can be retrieved and analysed. We validated the model by comparing responses to the cell wall lipids from Mycobacterium bovis bacillus Calmette-Guerin (BCG) to reported activities in other models. BCG lipid-coated beads and bone marrow-derived macrophages (input macrophages) were injected intraperitoneally into BALB/c mice. Input macrophages and recruited peritoneal exudate cells took up fluorescently tagged BCG lipids, and matrix-associated macrophages and neutrophils produced tumor necrosis factor, interleukin-1alpha, and interleukin-6. Leukocyte numbers and cytokine levels were greater in BCG lipid-bearing matrices than matrices containing non-coated or phosphatidylglycerol-coated beads. Leukocytes arrived in successive waves of neutrophils, macrophages and eosinophils, followed by NK and T cells (CD4(+), CD8(+), or gammadelta) at 7 days and B cells within 12 days. BCG lipids also predisposed matrices for adherence and vascularization, enhancing cellular recruitment. We submit that the matrix model presents pertinent features of the murine granulomatous response that will prove to be an adaptable method for study of this complex response.

  6. A Heterologous Multiepitope DNA Prime/Recombinant Protein Boost Immunisation Strategy for the Development of an Antiserum against Micrurus corallinus (Coral Snake Venom.

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    Henrique Roman Ramos

    2016-03-01

    Full Text Available Envenoming by coral snakes (Elapidae: Micrurus, although not abundant, represent a serious health threat in the Americas, especially because antivenoms are scarce. The development of adequate amounts of antielapidic serum for the treatment of accidents caused by snakes like Micrurus corallinus is a challenging task due to characteristics such as low venom yield, fossorial habit, relatively small sizes and ophiophagous diet. These features make it difficult to capture and keep these snakes in captivity for venom collection. Furthermore, there are reports of antivenom scarcity in USA, leading to an increase in morbidity and mortality, with patients needing to be intubated and ventilated while the toxin wears off. The development of an alternative method for the production of an antielapidic serum, with no need for snake collection and maintenance in captivity, would be a plausible solution for the antielapidic serum shortage.In this work we describe the mapping, by the SPOT-synthesis technique, of potential B-cell epitopes from five putative toxins from M. corallinus, which were used to design two multiepitope DNA strings for the genetic immunisation of female BALB/c mice. Results demonstrate that sera obtained from animals that were genetically immunised with these multiepitope constructs, followed by booster doses of recombinant proteins lead to a 60% survival in a lethal dose neutralisation assay.Here we describe that the genetic immunisation with a synthetic multiepitope gene followed by booster doses with recombinant protein is a promising approach to develop an alternative antielapidic serum against M. corallinus venom without the need of collection and the very challenging maintenance of these snakes in captivity.

  7. A Heterologous Multiepitope DNA Prime/Recombinant Protein Boost Immunisation Strategy for the Development of an Antiserum against Micrurus corallinus (Coral Snake) Venom

    Science.gov (United States)

    Ramos, Henrique Roman; Junqueira-de-Azevedo, Inácio de Loiola M.; Novo, Juliana Branco; Castro, Karen; Duarte, Clara Guerra; Machado-de-Ávila, Ricardo A.; Chavez-Olortegui, Carlos; Ho, Paulo Lee

    2016-01-01

    Background Envenoming by coral snakes (Elapidae: Micrurus), although not abundant, represent a serious health threat in the Americas, especially because antivenoms are scarce. The development of adequate amounts of antielapidic serum for the treatment of accidents caused by snakes like Micrurus corallinus is a challenging task due to characteristics such as low venom yield, fossorial habit, relatively small sizes and ophiophagous diet. These features make it difficult to capture and keep these snakes in captivity for venom collection. Furthermore, there are reports of antivenom scarcity in USA, leading to an increase in morbidity and mortality, with patients needing to be intubated and ventilated while the toxin wears off. The development of an alternative method for the production of an antielapidic serum, with no need for snake collection and maintenance in captivity, would be a plausible solution for the antielapidic serum shortage. Methods and Findings In this work we describe the mapping, by the SPOT-synthesis technique, of potential B-cell epitopes from five putative toxins from M. corallinus, which were used to design two multiepitope DNA strings for the genetic immunisation of female BALB/c mice. Results demonstrate that sera obtained from animals that were genetically immunised with these multiepitope constructs, followed by booster doses of recombinant proteins lead to a 60% survival in a lethal dose neutralisation assay. Conclusion Here we describe that the genetic immunisation with a synthetic multiepitope gene followed by booster doses with recombinant protein is a promising approach to develop an alternative antielapidic serum against M. corallinus venom without the need of collection and the very challenging maintenance of these snakes in captivity. PMID:26938217

  8. Immunisation of Sheep with Bovine Viral Diarrhoea Virus, E2 Protein Using a Freeze-Dried Hollow Silica Mesoporous Nanoparticle Formulation.

    Directory of Open Access Journals (Sweden)

    Donna Mahony

    Full Text Available Bovine viral diarrhoea virus 1 (BVDV-1 is arguably the most important viral disease of cattle. It is associated with reproductive, respiratory and chronic diseases in cattle across the world. In this study we have investigated the capacity of the major immunological determinant of BVDV-1, the E2 protein combined with hollow type mesoporous silica nanoparticles with surface amino functionalisation (HMSA, to stimulate immune responses in sheep. The current work also investigated the immunogenicity of the E2 nanoformulation before and after freeze-drying processes. The optimal excipient formulation for freeze-drying of the E2 nanoformulation was determined to be 5% trehalose and 1% glycine. This excipient formulation preserved both the E2 protein integrity and HMSA particle structure. Sheep were immunised three times at three week intervals by subcutaneous injection with 500 μg E2 adsorbed to 6.2 mg HMSA as either a non-freeze-dried or freeze-dried nanoformulation. The capacity of both nanovaccine formulations to generate humoral (antibody and cell-mediated responses in sheep were compared to the responses in sheep immunisation with Opti-E2 (500 μg together with the conventional adjuvant Quil-A (1 mg, a saponin from the Molina tree (Quillaja saponira. The level of the antibody responses detected to both the non-freeze-dried and freeze-dried Opti-E2/HMSA nanoformulations were similar to those obtained for Opti-E2 plus Quil-A, demonstrating the E2 nanoformulations were immunogenic in a large animal, and freeze-drying did not affect the immunogenicity of the E2 antigen. Importantly, it was demonstrated that the long term cell-mediated immune responses were detectable up to four months after immunisation. The cell-mediated immune responses were consistently high in all sheep immunised with the freeze-dried Opti-E2/HMSA nanovaccine formulation (>2,290 SFU/million cells compared to the non-freeze-dried nanovaccine formulation (213-500 SFU/million cells

  9. Factors influencing vaccination uptake. Workshop report. Current Australian research on the behavioural, social and demographic factors influencing immunisation, Royal Alexandra Hospital for Children, Sydney, March 1998.

    Science.gov (United States)

    Forrest, J M; Burgess, M A; McIntyre, P B

    2000-03-16

    Current Australian research on factors influencing vaccination was discussed at a workshop held at the Royal Alexandra Hospital for Children, Sydney, in March 1998, sponsored by the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS). The application of decision making theory to vaccination behaviour, the expectations and experiences of mothers, and reasons why parents fail to vaccinate their children were considered. Mothers' perceptions of the risks of vaccines, preferences of parents and providers for the mode of vaccine delivery, and community and social factors were all found to be part of the framework within which vaccination is accepted in Australia. Consumer considerations, media influences and overseas comparisons were discussed.

  10. Targeted routine antenatal anti-D prophylaxis in the prevention of RhD immunisation--outcome of a new antenatal screening and prevention program.

    Directory of Open Access Journals (Sweden)

    Eleonor Tiblad

    Full Text Available OBJECTIVE: To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP. MATERIALS AND METHODS: We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250-300 µg was administered intramuscularly in gestational week 28-30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy. RESULTS: During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61% were RHD positive and 3270 (39% RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380 (95% CI 0.15-0.36% compared to 0.46 percent (86/18546 (95% CI 0.37 to 0.56% in the reference cohort. The risk ratio (RR for sensitisation was 0.55 (95% CI 0.35 to 0.87 and the risk reduction was statistically significant (p = 0.009. The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT of 500. CONCLUSIONS: Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this

  11. Composition and immunoreactivity of the A60 complex and other cell fractions from Mycobacterium bovis BCG.

    Science.gov (United States)

    Cocito, C; Vanlinden, F

    1995-02-01

    Surface static cultures of Mycobacterium bovis BCG contained cells embedded in an extracellular matrix, whose mechanical removal yielded free cells that were pressure disrupted and fractionated into cytoplasm and walls. Cell envelopes were either mechanically disrupted or extracted with detergents. Intracellular and extracellular fractions were analysed for proteins, polysaccharides, and antigen 6O (A60), a major complex immunodominant in tuberculosis. A60 was present in extracellular matrix, cytoplasm and walls: it represented a substantial portion of the proteins and polysaccharides of these fractions. While the protein/polysaccharide ratio varied according to the origin of A60 preparations, the electrophoretic patterns of A60 proteins (which accounted for the immunogenicity of the complex) remained unchanged. Western blots pointed to the proteins present within the 29-45 kDa range as the A60 components endowed with the highest immunogenicity level. Since the most heavily stained protein bands in SDS-PAGE patterns were located outside the region best recognized by antisera, a striking discordance was found between concentration and immunogenicity patterns of A60 proteins. The electrophoretic patterns of A60- and non-A60-proteins from cytoplasm were also different. A60 complexes in dot blots and some electrophoresed A60 proteins reacted with monoclonal antibodies directed against lipoarabinomannan (LAM), a highly immunogenic polymer of cell envelope. This contaminating compound was removed from A60 with organic solvents and detergents. SDS-PAGE and Western blot patterns of proteins from delipidated A60 were similar to those of native A60 proteins.

  12. Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high-risk cohort: A prospective study of allergy-prone children from birth to six years.

    Science.gov (United States)

    Thomson, Jennifer A; Widjaja, Constance; Darmaputra, Abbi A P; Lowe, Adrian; Matheson, Melanie C; Bennett, Catherine M; Allen, Katrina; Abramson, Michael J; Hosking, Cliff; Hill, David; Dharmage, Shyamali C

    2010-11-01

    The role of early childhood infections and immunisation in the development of allergic diseases remains controversial. To examine these associations, six hundred and twenty infants with first-degree relatives with allergic diseases were recruited into the Melbourne Atopy Cohort Study. Information on risk factors and outcomes was collected by interviewer administered questionnaire and was based on parental report and/or a physician's diagnosis. Risk factors examined included early childhood infections (including gastroenteritis, otitis media and lower respiratory tract infections) and immunisations in the first 2 yr of life. Outcomes were current asthma, allergic rhinitis and eczema at 6 yr of age. Univariate and multivariate regression analysis were used to estimate relative risk (RR) and assess confounding. By 6 yr, 79% of the original cohort remained in the study. Those with at least three episodes of gastroenteritis showed an increased risk (crude RR 2.36, 95%CI 1.41 3.95; adjusted RR 2.03 95%CI 1.50 2.75) for the later development of asthma at age 6. Of the scheduled immunisations, Sabin immunisation in the second year had a reduced risk of asthma at 6 yr (crude RR 0.60, 95%CI 0.37 0.98; adjusted RR 0.63 95%CI 0.39 1.02). Combined diphtheria and tetanus (CDT) immunisation in the first year had an increased risk of asthma at 6 yr (RR 1.76, 95%CI 1.11 2.78; adjusted RR 1.88 95%CI 1.28 2.77). Recurrent gastroenteritis in early childhood is associated with a later risk of asthma. This may reflect a cause and effect relationship, or exposure to common risk factors. In contrast, Sabin immunisation in the second year is associated with a decreased risk of asthma in later childhood. CDT immunisation in the first year may be a risk factor for asthma, but the need for CDT immunisation may also be a marker of increased risk of asthma in later childhood.

  13. Valor preditivo do teste tuberculínico padronizado em crianças vacinadas com BCG

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1992-08-01

    Full Text Available A aplicabilidade do teste tuberculínico em crianças menores de 5 anos vacinadas com BCG é assunto controvertido. Visando contribuir para esclarecê-lo foi analisado o valor preditivo positivo do teste tuberculínico padronizado em população sob elevada cobertura vacinal e baixa prevalência de infecção tuberculosa. A partir da proporção de reatores fortes em lactentes e escolares vacinados e não vacinados, foram calculadas a razão de declínio da alergia tuberculínica nos vacinados e a razão de crescimento nos não vacinados, o que possibilitou a estimativa dos respectivos valores nas idades intermediárias. A expectativa de falsos-positivos (FP foi então calculada por diferença. Conhecidas a sensibilidade e a especificidade do teste (E=1-FP, a cobertura BCG e a prevalência de infecção, os valores preditivos (para a infecção tuberculosa foram: 1,52%, 4,22%, 8,26%, 14,86% e 23,00%, do primeiro ao quinto ano de vida. Nessas condições, a probabilidade de uma reação forte ser devida ao BCG é grande, especialmente nos dois primeiros anos, o que reduz a aplicabilidade clínica e epidemiológica do teste.

  14. Multivalent TB vaccines targeting the esx gene family generate potent and broad cell-mediated immune responses superior to BCG.

    Science.gov (United States)

    Villarreal, Daniel O; Walters, Jewell; Laddy, Dominick J; Yan, Jian; Weiner, David B

    2014-01-01

    Development of a broad-spectrum synthetic vaccine against TB would represent an important advance to the limited vaccine armamentarium against TB. It is believed that the esx family of TB antigens may represent important vaccine candidates. However, only 4 esx antigens have been studied as potential vaccine antigens. The challenge remains to develop a vaccine that simultaneously targets all 23 members of the esx family to induce enhanced broad-spectrum cell-mediated immunity. We sought to investigate if broader cellular immune responses could be induced using a multivalent DNA vaccine representing the esx family protein members delivered via electroporation. In this study, 15 designed esx antigens were created to cross target all members of the esx family. They were distributed into groups of 3 self-processing antigens each, resulting in 5 trivalent highly optimized DNA plasmids. Vaccination with all 5 constructs elicited robust antigen-specific IFN-γ responses to all encoded esx antigens and induced multifunctional CD4 Th1 and CD8 T cell responses. Importantly, we show that when all constructs are combined into a cocktail, the RSQ-15 vaccine, elicited substantial broad Ag-specific T cell responses to all esx antigens as compared with vaccination with BCG. Moreover, these vaccine-induced responses were highly cross-reactive with BCG encoded esx family members and were highly immune effective in a BCG DNA prime-boost format. Furthermore, we demonstrate the vaccine potential and immunopotent profile of several novel esx antigens never previously studied. These data highlight the likely importance of these novel immunogens for study as preventative or therapeutic synthetic TB vaccines in combination or as stand alone antigens.

  15. Complement factor H interferes with Mycobacterium bovis BCG entry into macrophages and modulates the pro-inflammatory cytokine response.

    Science.gov (United States)

    Abdul-Aziz, Munirah; Tsolaki, Anthony G; Kouser, Lubna; Carroll, Maria V; Al-Ahdal, Mohammed N; Sim, Robert B; Kishore, Uday

    2016-09-01

    Mycobacterium tuberculosis is an accomplished intracellular pathogen, particularly within the macrophage and this is of the utmost importance in the host-pathogen stand-off observed in the granuloma during latent tuberculosis. Contact with innate immune molecules is one of the primary interactions that can occur with the pathogen M. tuberculosis once inhaled. Complement proteins may play a role in facilitating M. tuberculosis interactions with macrophages. Here, we demonstrate that factor H, a complement regulatory protein that down-regulates complement alternative pathway activation, binds directly to the model organism M. bovis BCG. Binding of factor H reaches saturation at 5-10μg of factor H/ml, well below the plasma level. C4 binding protein (C4BP) competed with factor H for binding to mycobacteria. Factor H was also found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Real-time qPCR analysis showed stark differential responses of pro- and anti-inflammatory cytokines during the early stages of phagocytosis, as evident from elevated levels of TNF-α, IL-1β and IL-6, and a concomitant decrease in IL-10, TGF-β and IL-12 levels, when THP-1:BCG interaction took place in the presence of factor H. Our results suggest that factor H can interfere with mycobacterial entry into macrophages and modulate inflammatory cytokine responses, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. Our results offer novel insights into complement activation-independent functions of factor H during the host-pathogen interaction in tuberculosis.

  16. Structural features of lipoarabinomannan from Mycobacterium bovis BCG. Determination of molecular mass by laser desorption mass spectrometry.

    Science.gov (United States)

    Venisse, A; Berjeaud, J M; Chaurand, P; Gilleron, M; Puzo, G

    1993-06-15

    It was recently shown that mycobacterial lipoarabinomannan (LAM) can be classified into two types (Chatterjee, D., Lowell, K., Rivoire B., McNeil M. R., and Brennan, P. J. (1992) J. Biol. Chem. 267, 6234-6239) according to the presence or absence of mannosyl residues (Manp) located at the nonreducing end of the oligoarabinosyl side chains. These two types of LAM were found in a pathogenic Mycobacterium tuberculosis strain and in an avirulent M. tuberculosis strain, respectively, suggesting that LAM with Manp characterizes virulent and "disease-inducing strains." We now report the structure of the LAM from Mycobacterium bovis Bacille Calmette-Guérin (BCG) strain Pasteur, largely used throughout the world as vaccine against tuberculosis. Using an up-to-date analytical approach, we found that the LAM of M. bovis BCG belongs to the class of LAMs capped with Manp. By means of two-dimensional homonuclear and heteronuclear scalar coupling NMR analysis and methylation data, the sugar spin system assignments were partially established, revealing that the LAM contained two types of terminal Manp and 2-O-linked Manp. From the following four-step process: (i) partial hydrolysis of deacylated LAM (dLAM), (ii) oligosaccharide derivatization with aminobenzoic ethyl ester, (iii) HPLC purification, (iv) FAB/MS-MS analysis; it was shown that the dimannosyl unit alpha-D-Manp-(1-->2)-alpha-D-Manp is the major residue capping the termini of the arabinan of the LAM. In this report, LAM molecular mass determination was established using matrix-assisted UV-laser desorption/ionization mass spectrometry which reveals that the LAM molecular mass is around 17.4 kDa. The similarity of the LAM structures between M. bovis BCG and M. tuberculosis H37Rv is discussed in regard to their function in the immunopathology of mycobacterial infection.

  17. The Mean and Scatter of the Velocity Dispersion-Optical Richness Relation for MaxBCG Galaxy Clusters

    Energy Technology Data Exchange (ETDEWEB)

    Becker, M.R.; McKay, T.A.; /Michigan U.; Koester, B.; /Chicago U., Astron. Astrophys. Ctr.; Wechsler, R.H.; /KIPAC, Menlo Park /SLAC /Stanford U., Phys. Dept.; Rozo, E.; /Ohio State U.; Evrard, A.; /Michigan U. /Michigan U., MCTP; Johnston, D.; /Caltech, JPL; Sheldon, E.; /New York U.; Annis, J.; /Fermilab; Lau, E.; /Chicago U., Astron. Astrophys. Ctr.; Nichol, R.; /Portsmouth U., ICG; Miller, C.; /Michigan U.

    2007-06-05

    The distribution of galaxies in position and velocity around the centers of galaxy clusters encodes important information about cluster mass and structure. Using the maxBCG galaxy cluster catalog identified from imaging data obtained in the Sloan Digital Sky Survey, we study the BCG--galaxy velocity correlation function. By modeling its non-Gaussianity, we measure the mean and scatter in velocity dispersion at fixed richness. The mean velocity dispersion increases from 202 {+-} 10 km s{sup -1} for small groups to more than 854 {+-} 102 km s{sup -1} for large clusters. We show the scatter to be at most 40.5{+-}3.5%, declining to 14.9{+-}9.4% in the richest bins. We test our methods in the C4 cluster catalog, a spectroscopic cluster catalog produced from the Sloan Digital Sky Survey DR2 spectroscopic sample, and in mock galaxy catalogs constructed from N-body simulations. Our methods are robust, measuring the scatter to well within one-sigma of the true value, and the mean to within 10%, in the mock catalogs. By convolving the scatter in velocity dispersion at fixed richness with the observed richness space density function, we measure the velocity dispersion function of the maxBCG galaxy clusters. Although velocity dispersion and richness do not form a true mass--observable relation, the relationship between velocity dispersion and mass is theoretically well characterized and has low scatter. Thus our results provide a key link between theory and observations up to the velocity bias between dark matter and galaxies.

  18. Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial

    DEFF Research Database (Denmark)

    Nørrelykke Nissen, Thomas; Birk, Nina Marie; Kjærgaard, Jesper;

    2016-01-01

    OBJECTIVE: To evaluate adverse reactions of the Bacillus Calmette-Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial. DESIGN: A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no inter...

  19. Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial

    DEFF Research Database (Denmark)

    Diness, B.R.; Roth, A.; Nante, E.;

    2008-01-01

    Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Design Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering...... approximately 90 000 inhabitants. Participants 4345 infants due to receive BCG. Intervention Infants were randomised to 50 000 IU vitamin A or placebo and followed until age 12 months. Main outcome measure Mortality rate ratios. Results 174 children died during follow-up (mortality=47/ 1000 person.......84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African...

  20. The results of treatments and complications of immunotherapy (BCG and alpha-interferon in superficial TCC of bladder

    Directory of Open Access Journals (Sweden)

    Jabalameli P

    1994-04-01

    Full Text Available The treatment of choice for bladder tumors is TUR, but because of high incidence of recurrence in these tumors, various treatments are suggested. In one study, 32 patients involved with superficial T.C.C. of bladder selected and divided in two equal groups. In the first group, after T.U.R, 10 million IU of a alpha-interferon was injected into the bladder through a catheter and in the other group, after TUR, they treated with injection of BCG into bladders. The results of these two drugs in prevention of recurrence and their side effects were studied and compaired

  1. Impact of PGL-I seropositivity on the protective effect of BCG vaccination among leprosy contacts: a cohort study.

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    Nádia C Düppre

    Full Text Available BACKGROUND: Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG vaccination after index case diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135 leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR = 4.1; 95% CI: 1.8-8.2 compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2-8.1. The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6 occurred in PGL-I-positive unvaccinated contacts. CONCLUSION: Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index

  2. Strategic analysis of PKM Duda SA. on Polish meat market with the application of BCG growth-share matrix

    OpenAIRE

    Anna Zielińska-Chmielewska

    2012-01-01

    The main goal of this paper was to examine the market position of one leading meat processing enterprise PKM Duda SA. on the domestic meat market. The assessment of the activity portfolio on its three strategic units was undertaken with the usage of BCG matrix. The PKM Duda SA. was chosen for the study because: a) processes more than 20 tons of slaughter per week, b) is located in the country of origin, c) exists on Warsaw Stock Exchange Market, d) preserves continuity of its database in Moni...

  3. Time Delay Cosmography

    CERN Document Server

    Treu, Tommaso

    2016-01-01

    Gravitational time delays, observed in strong lens systems where the variable background source is multiply-imaged by a massive galaxy in the foreground, provide direct measurements of cosmological distance that are very complementary to other cosmographic probes. The success of the technique depends on the availability and size of a suitable sample of lensed quasars or supernovae, precise measurements of the time delays, accurate modeling of the gravitational potential of the main deflector, and our ability to characterize the distribution of mass along the line of sight to the source. We review the progress made during the last 15 years, during which the first competitive cosmological inferences with time delays were made, and look ahead to the potential of significantly larger lens samples in the near future.

  4. Delayed Random Relays

    CERN Document Server

    Ohira, Toru

    2016-01-01

    We present here a system with collection of random walks relaying a signal in one dimension with a presence of a delay. We are interested in the time for a signal to travel from one end (start) to the other end (finish) of the lined group of random walkers. It is found that there is an optimal number of walkers for the signal to travel fastest if the delay is present. We discuss implications of this model and associated behaviors to physical and biological systems.

  5. Approximation of distributed delays

    CERN Document Server

    Lu, Hao; Eberard, Damien; Simon, Jean-Pierre

    2010-01-01

    We address in this paper the approximation problem of distributed delays. Such elements are convolution operators with kernel having bounded support, and appear in the control of time-delay systems. From the rich literature on this topic, we propose a general methodology to achieve such an approximation. For this, we enclose the approximation problem in the graph topology, and work with the norm defined over the convolution Banach algebra. The class of rational approximates is described, and a constructive approximation is proposed. Analysis in time and frequency domains is provided. This methodology is illustrated on the stabilization control problem, for which simulations results show the effectiveness of the proposed methodology.

  6. Successive Intramuscular Boosting with IFN-Alpha Protects Mycobacterium bovis BCG-Vaccinated Mice against M. lepraemurium Infection

    Directory of Open Access Journals (Sweden)

    G. G. Guerrero

    2015-01-01

    Full Text Available Leprosy caused by Mycobacterium leprae primarily affects the skin and peripheral nerves. As a human infectious disease, it is still a significant health and economic burden on developing countries. Although multidrug therapy is reducing the number of active cases to approximately 0.5 million, the number of cases per year is not declining. Therefore, alternative host-directed strategies should be addressed to improve treatment efficacy and outcome. In this work, using murine leprosy as a model, a very similar granulomatous skin lesion to human leprosy, we have found that successive IFN-alpha boosting protects BCG-vaccinated mice against M. lepraemurium infection. No difference in the seric isotype and all IgG subclasses measured, neither in the TH1 nor in the TH2 type cytokine production, was seen. However, an enhanced iNOS/NO production in BCG-vaccinated/i.m. IFN-alpha boosted mice was observed. The data provided in this study suggest a promising use for IFN-alpha boosting as a new prophylactic alternative to be explored in human leprosy by targeting host innate cell response.

  7. The XXL survey XV: Evidence for dry merger driven BCG growth in XXL-100-GC X-ray clusters

    CERN Document Server

    Lavoie, S; Democles, J; Eckert, D; Gastaldello, F; Smith, G P; Lidman, C; Adami, C; Pacaud, F; Pierre, M; Clerc, N; Giles, P; Lieu, M; Chiappetti, L; Altieri, B; Ardila, F; Baldry, I; Bongiorno, A; Desai, S; Elyiv, A; Faccioli, L; Gardner, B; Garilli, B; Groote, M W; Guennou, L; Guzzo, L; Hopkins, A M; Liske, J; McGee, S; Melnyk, O; Owers, M S; Poggianti, B; Ponman, T J; Scodeggio, M; Spitler, L; Tuffs, R J

    2016-01-01

    The growth of brightest cluster galaxies is closely related to the properties of their host cluster. We present evidence for dry mergers as the dominant source of BCG mass growth at $z\\lesssim1$ in the XXL 100 brightest cluster sample. We use the global red sequence, H$\\alpha$ emission and mean star formation history to show that BCGs in the sample possess star formation levels comparable to field ellipticals of similar stellar mass and redshift. XXL 100 brightest clusters are less massive on average than those in other X-ray selected samples such as LoCuSS or HIFLUGCS. Few clusters in the sample display high central gas concentration, rendering inefficient the growth of BCGs via star formation resulting from the accretion of cool gas. Using measures of the relaxation state of their host clusters, we show that BCGs grow as relaxation proceeds. We find that the BCG stellar mass corresponds to a relatively constant fraction 1\\%\\ of the total cluster mass in relaxed systems. We also show that, following a cluste...

  8. Vaccine-associated paralytic poliomyelitis and BCG-osis in an immigrant child with severe combined immunodeficiency syndrome - Texas, 2013.

    Science.gov (United States)

    Trimble, Robert; Atkins, Jane; Quigg, Troy C; Burns, Cara C; Wallace, Gregory S; Thomas, Mary; Mangla, Anil T; Infante, Anthony J

    2014-08-22

    Poliovirus transmission has been eliminated in most of the world through the use of inactivated poliovirus vaccine (IPV) and live, attenuated oral poliovirus vaccine (OPV). In the United States, use of OPV was discontinued by the year 2000 because of the potential for vaccine-associated paralytic polio (VAPP); an average of eight cases were reported each year in the United States during 1980-2000. Polio eradication efforts in other parts of the world continue to rely on OPV to take advantage of transmission of poliovirus vaccine strains to unvaccinated persons in the population, lower cost, and ease of administration. In 2013, an infant aged 7 months who recently immigrated to the United States from India was referred to a hospital in San Antonio, Texas. The infant had fever, an enlarging skin lesion in the deltoid region with axillary lymphadenopathy, decreased activity, and inability to bear weight on the left leg, progressing to paralysis of the left leg over a 6-week period. Recognition of lymphopenia on complete blood count led to immune evaluation, which revealed the presence of severe combined immunodeficiency syndrome (SCIDS), an inherited disorder. A history of OPV and bacille Calmette-Guérin (BCG) vaccination in India led to the diagnoses of VAPP and BCG-osis, which were confirmed microbiologically. This report demonstrates the importance of obtaining a comprehensive clinical history in a child who has recently immigrated to the United States, with recognition that differing vaccine practices in other countries might require additional consideration of potential etiologies.

  9. Strategic analysis of PKM Duda SA. on Polish meat market with the application of BCG growth-share matrix

    Directory of Open Access Journals (Sweden)

    Anna Zielińska-Chmielewska

    2012-01-01

    Full Text Available The main goal of this paper was to examine the market position of one leading meat processing enterprise PKM Duda SA. on the domestic meat market. The assessment of the activity portfolio on its three strategic units was undertaken with the usage of BCG matrix. The PKM Duda SA. was chosen for the study because: a processes more than 20 tons of slaughter per week, b is located in the country of origin, c exists on Warsaw Stock Exchange Market, d preserves continuity of its database in Monitor Polski „B”. The analysis proved that all three examined strategic units have different market shares and operate on markets of a different acceleration. The highest income rate brings the meat processing unit (B, the lowest slaughter unit (A. The market position of PKM Duda SA. can be improved when a retail trade unit (B moves away from question marks into stars. Although BCG matrix draws a fast and a complex strategic situation, is not free from disadvantages. That is the reason why further, also portfolio, analysis should be im-plemented.

  10. Delayed traumatic diaphragmatic hernia

    Science.gov (United States)

    Lu, Jing; Wang, Bo; Che, Xiangming; Li, Xuqi; Qiu, Guanglin; He, Shicai; Fan, Lin

    2016-01-01

    Abstract Background: Traumatic diaphragmatic hernias (TDHs) are sometimes difficult to identify at an early stage and can consequently result in diagnostic delays with life-threatening outcomes. It is the aim of this case study to highlight the difficulties encountered with the earlier detection of traumatic diaphragmatic hernias. Methods: Clinical data of patients who received treatment for delayed traumatic diaphragmatic hernias in registers of the First Affiliated Hospital of Xi’an Jiaotong University from 1998 to 2014 were analyzed retrospectively. Results: Six patients were included in this study. Left hemidiaphragm was affected in all of them. Most of the patients had a history of traffic accident and 1 a stab-penetrating injury. The interval from injury to developing symptoms ranged from 2 to 11 years (median 5 years). The hernial contents included the stomach, omentum, small intestine, and colon. Diaphragmatic injury was missed in all of them during the initial managements. All patients received operations once the diagnosis of delayed TDH was confirmed, and no postoperative mortality was detected. Conclusions: Delayed TDHs are not common, but can lead to serious consequences once occurred. Early detection of diaphragmatic injuries is crucial. Surgeons should maintain a high suspicion for injuries of the diaphragm in cases with abdominal or lower chest traumas, especially in the initial surgical explorations. We emphasize the need for radiographical follow-up to detect diaphragmatic injuries at an earlier stage. PMID:27512848

  11. Delayed breast implant reconstruction

    DEFF Research Database (Denmark)

    Hvilsom, Gitte B.; Hölmich, Lisbet R.; Steding-Jessen, Marianne;

    2012-01-01

    We evaluated the association between radiation therapy and severe capsular contracture or reoperation after 717 delayed breast implant reconstruction procedures (288 1- and 429 2-stage procedures) identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during...... reconstruction approaches other than implants should be seriously considered among women who have received radiation therapy....

  12. Permissible Delay in Payments

    Directory of Open Access Journals (Sweden)

    Yung-Fu Huang

    2007-01-01

    Full Text Available The main purpose of this paper wants to investigate the optimal retailer's lot-sizing policy with two warehouses under partially permissible delay in payments within the economic order quantity (EOQ framework. In this paper, we want to extend that fully permissible delay in payments to the supplier would offer the retailer partially permissible delay in payments. That is, the retailer must make a partial payment to the supplier when the order is received. Then the retailer must pay off the remaining balance at the end of the permissible delay period. In addition, we want to add the assumption that the retailer's storage space is limited. That is, the retailer will rent the warehouse to store these exceeding items when the order quantity is larger than retailer's storage space. Under these conditions, we model the retailer's inventory system as a cost minimization problem to determine the retailer's optimal cycle time and optimal order quantity. Three theorems are developed to efficiently determine the optimal replenishment policy for the retailer. Finally, numerical examples are given to illustrate these theorems and obtained a lot of managerial insights.

  13. 'No delays achiever'.

    Science.gov (United States)

    2007-05-01

    The latest version of the NHS Institute for Innovation and Improvement's 'no delays achiever', a web based tool created to help NHS organisations achieve the 18-week target for GP referrals to first treatment, is available at www.nodelaysachiever.nhs.uk.

  14. Evaluation of BCG Vaccination in Neonatal%新生儿卡介苗接种效果评价

    Institute of Scientific and Technical Information of China (English)

    段俊霞

    2012-01-01

    Objective:o investigate the situation of neonatal BCG vaccination in our city,evaluate the vaccination quality and results,and analysis its impact factor.Methods:Analysis the the number of BCG vaccination cases in April 2006 to April 2010 and the number of live births over the same period,analysis vaccination rates in different demographic. And investigation neonatal BCG vaccination after 12 weeks of PPD positive rate,analysis of different kinds of time in early seroconversion rate differences.Results:The total of live births in the city in April 2006 to April 2010 was 10421 cases and neonatal BCG early species of 10059 cases,the total rate of 96.56% in early types.Among them,the early species of the city' s population rate (96.75%) was higher than the initial species field population rate (95.74%).PPD test 3433 cases,the positive rate 95.66%,of which the baby' s positive rate (95.65%) and girls (95.10%) showed no significant difference.The cards scar group PPD test positive rate (96.40%) was significantly higher than non-card scar group (92.67%),the relative odds ratio was 2.121.Kinds of time in early January and the PPD test positive rate (97.02%) was significantly higher than the first time kind of positive rates greater than 1 month (52%),the relative odds ratio was 30.014.Conclusion:The city' s overall neonatal BCG vaccination rate was higher, reaching the state level,but should strengthen the floating population of foreign publicity and vaccination. And care to emphasize the importance of early vaccination.%目的:调查我市新生儿卡介苗接种情况,评价接种质量及效果,并分析其影响因素.方法:收集2006~2010年在我市接种卡介苗例数及同期活产数,分析不同人口构成的接种率差异.并调查12周后卡介苗接种新生儿的PPD阳转率,分析不同初种时间的阳转率差异.结果:2006年4月~2010年4月我市共有活产新生儿10421例,卡介苗初种10059例,总初种率96.56%.

  15. Neutralisation of venom-induced haemorrhage by IgG from camels and llamas immunised with viper venom and also by endogenous, non-IgG components in camelid sera

    NARCIS (Netherlands)

    Harrison, R.A.; Hasson, S.S.; Harmsen, M.M.; Laing, G.D.; Theakston, R.D.

    2006-01-01

    Envenoming by snakes results in severe systemic and local pathology. Intravenous administration of antivenom, prepared from IgG of venom immunised horses or sheep, is the only effective treatment of systemic envenoming. Conventional antivenoms, formulated as intact IgG, papain-cleaved (Fab) or pepsi

  16. Construction and expression of a recombinant BCG-TSOL18 vaccine of Taenia solium%猪带绦虫重组 BCG-TSOL18疫苗构建及其表达

    Institute of Scientific and Technical Information of China (English)

    杨凤娇; 周必英

    2015-01-01

    We constructed a recombinant Bacillus Calmette‐Guerin(BCG)‐TSOL18 vaccine of Taenia solium and observed the expression of the TSOL18 gene in BCG .The TSOL18 gene of Taenia solium was obtained from the recombinant plasmid pGEX‐TSOL18 by digestion method and cloned into Escherichia coli (E .coli)‐mycobacterium shuttle plasmid pMV261 to con‐struct the recombinant plasmid pMV261‐TSOL18 of Taenia solium ,and the recombinant plasmid was identified by restriction enzyme digestion ,PCR and DNA sequencing .Then ,the recombinant plasmid was transformed into BCG by electroporation to construct the recombinant BCG‐TSOL18 vaccine of Taenia solium ,and the vaccine was identified by PCR .The expression of the TSOL18 gene in BCG was identified by SDS‐PAGE and Western blot .The 393 bp TSOL18 gene fragment was successfully obtained by restriction enzyme digestion .Restriction enzyme digestion ,PCR and DNA sequencing suggested that the recombi‐nant plasmid pMV261‐TSOL18 of Taenia solium was successfully constructed .PCR confirmed that the recombinant plasmid pMV261‐TSOL18 of Taenia solium was successfully transformed into BCG ,suggesting that the recombinant BCG‐TSOL18 vaccine of Taenia solium was successfully constructed .SDS‐PAGE showed that the relative molecular mass (Mr) of TSOL18 target protein was approximately 14 .7 kD .Results of western blot showed the TSOL18 target protein could be recognized by rabbit antiserum or cysticercosis swine serum .The recombinant BCG‐TSOL18 vaccine of Taenia solium was successfully con‐structed .The TSOL18 gene of Taeniasolium was successfully expressed in BCG and the expressed TSOL18 recombinant pro‐tein had specific antigenicity .This result would lay a foundation for further study of the vaccine .%目的:构建猪带绦虫重组BCG‐TSOL18疫苗,研究TSOL18基因在BCG中的表达情况。方法通过酶切的方法从重组质粒pGEX‐TSOL18获取猪带绦虫TSOL18基因,将其定向克隆到大肠

  17. Family history of immigration from a tuberculosis endemic country and low family income are associated with a higher BCG vaccination coverage in Ile-de-France region, France.

    Science.gov (United States)

    Guthmann, Jean-Paul; Chauvin, Pierre; Le Strat, Yann; Soler, Marion; Fonteneau, Laure; Lévy-Bruhl, Daniel

    2013-11-19

    After withdrawal of multipuncture BCG device from the French market in January 2006, vaccination coverage (VC) with the intradermal device has dropped and since remained sub-optimal in Ile-de-France, the only region of mainland France where BCG is recommended to all children. We conducted a cross-sectional study to identify socio-economic factors associated with BCG VC in children of Paris metropolitan area born after January 2006. Two-stage random sampling was used to include 425 children up to 5 years old from Paris and its suburbs. Information was collected through face-to-face interviews and vaccination status confirmed by a vaccination document. Poisson regression analyzed the association between VC and potential determinants. VC of children from families with the lowest incomes (first quartile of family income/consumption unit (CU) (history of immigration, regardless of family income, are correctly identified as being at high risk of tuberculosis and properly vaccinated with BCG in this area.

  18. Sex-differential effect on infant mortality of oral polio vaccine administered with BCG at birth in Guinea-Bissau. A natural experiment

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Fisker, Ane Baerent; Rodrigues, Amabelia;

    2008-01-01

    was not available during several periods. We took advantage of this "natural experiment" to test the effect on mortality of receiving OPV at birth. METHODOLOGY: Between 2002 and 2004, the VAS trial randomised normal-birth-weight infants to 50,000 IU VAS or placebo administered with BCG. Provision of OPV at birth...

  19. Synthetic oligonucleotides with particular base sequences from the cDNA encoding proteins of Mycobacterium bovis BCG induce interferons and activate natural killer cells.

    Science.gov (United States)

    Tokunaga, T; Yano, O; Kuramoto, E; Kimura, Y; Yamamoto, T; Kataoka, T; Yamamoto, S

    1992-01-01

    Thirteen kinds of 45-mer single-stranded oligonucleotide, having sequence randomly selected from the known cDNA encoding BCG proteins, were tested for their capability to augment natural killer (NK) cell activity of mouse spleen cells in vitro. Six out of the 13 oligonucleotides showed the activity, while the others did not. In order to know the minimal and essential sequence(s) responsible for the biological activity, 2 kinds of 30-mer and 5 kinds of 15-mer oligonucleotide fragments of an active 45-mer nucleotide were tested for their activity. One of the 30-mer oligonucleotides, designated BCG-A4a, was active, but the other 30-mer was inactive. All of the 15-mer oligonucleotide fragments were inactive. The BCG-A4a also stimulated the spleen cells to produce interferon (IFN)-alpha and -gamma. An experiment using anti-IFN antisera showed that the NK cell activation by the oligonucleotide was ascribed to the IFN-alpha produced. It was noticed that all of the biologically active oligonucleotides possessed one or more palindrome sequence(s), and the inactive ones did not, with an exception of a 45-mer inactive oligonucleotide containing overlapping palindrome sequences (GGGCCCGGG). These findings strongly suggest that certain palindrome sequences, like GACGTC, GGCGCC and TGCGCA, are essential for 30-mer oligonucleotides, like BCG-A4a, to induce IFNs.

  20. Mycotic aneurysm of the popliteal artery as a complication of intravesical BCG therapy for superficial bladder cancer. Case report and literature review.

    NARCIS (Netherlands)

    Witjes, J.A.; Vriesema, J.L.J.; Brinkman, K.; Bootsma, G.P.; Barentsz, J.O.

    2003-01-01

    A 67-year-old man was treated with maintenance intravesical BCG for superficial bladder cancer. As a culture-proven complication of this therapy, he developed general malaise, high fever, granulomatous hepatitis and a mycotic aneurysm in his left knee. All complications were treated successfully wit

  1. [Bacillus Calmette-Guérin (BCG) disease and interleukin 12 receptor β1 deficiency: clinical experience of two familial and one sporadic case].

    Science.gov (United States)

    Strickler, Alexis; Pérez, Amir; Risco, Migdy; Gallo, Silvanna

    2014-08-01

    BCG disease has been reported in primary and secondary immunodeficiency and as Mendelian Susceptibility to Mycobacterial Diseases (MSMD). Investigation of this syndrome has led to the identifications of a series of genetic, inherited defects in the IL-12/IFN-γ axis. MSMD-causing mutations have been found in seven autosomal and two X-linked genes. In these patients, local or disseminated vaccine BCG infections are common. We report a clinical series including two infants with left axillary adenitis ipsilateral to the site of neonatal BCG immunization; one of them member of a family with two previously reported cases and a single sporadic case. All of them were diagnosed sequentially in Puerto Montt, Chile. The aim of this report is to notify the first Chilean disseminated BCG patients without previous immunodeficiency, in whom it was possible to identify an underlying immunodeficiency, although specific tests for IL-12/IFN-γ axis was no performed in our country. Clinical suspicion and international collaboration permitted to confirm IL12-Rβ1 deficiency in 2 of 3 familial cases and a sporadic case.

  2. Delay-independent stabilization for teleoperation with time varying delay

    OpenAIRE

    Fujita, Hiroyuki; Namerikawa, Toru

    2009-01-01

    This paper deals with the stability for nonlinear teleoperation with time varying communication delays. The proposed method is passivity-based controllers with time varying gains which depend on the rate of change of time varying delay. In our proposed method, stability condition is independent of the magnitude of the communication delay and the damping of the system. The delay-independent stability is shown via Lyapunov stability methods. Several experimental results show the effectiveness o...

  3. Comparative Study on the Immunogenicity between Recombinant MS-Sj26GST Vaccine and Recombinant BCG-Sj26GST Vaccine in Schistosoma japonicum

    Institute of Scientific and Technical Information of China (English)

    戴五星; 高红; 黄海浪; 袁野; 胡佳杰; 皇甫永穆

    2003-01-01

    The BALB/c mice were immunized with rMS-Sj26GST and rBCG-Sj26GST vaccine inSchistosoma japonicum by subcutaneous injection. After they were immunized for 8 weeks, the eye-balls were removed to get blood and macrophages of abdominal cavity and spleen cells were harves-ted. The lymphocytic stimulating index (SI) was used to measure the cellular proliferating abilityand NO release was used to measure the phagocytic activity of the macrophages. By using ELISAkit, the levels of interleukin-2 (IL-2) and interferon-γ(IFN-γ) in serum and the splenic lymphocyt-ic cultured supernatant were detected. The results showed that after the mice were immunized with106 CFU of rMS-Sj26GST and rBCG-Sj26GST vaccine separately by subcutaneous injection, prolif-erating ability of splenic lymphocytes in the mice showed no difference (P>0.05), but both weresignificantly increased as compared with that in the control group(P<0.05); The contents of NOin the intraperitoneal macrophages of rMS-Sj26GST vaccine group were significantly lower than inthe control group (P<0. 001) and rBCG-Sj26GST vaccine group (P<0. 01); The levels of serumIL-2 in the rMS-Sj26GST vaccine group were significantly increased as compared with that in thecontrol group (P<0. 001), vector group (P<0.01) and rBCG-Sj26GST vaccine group (P<0.05);The contents of serum IFN-γ in the rMS-Sj26GST vaccine group were significantly increased ascompared with that in the control group (P<0.01) and rBCG-Sj26GST vaccine group (P<0.05).The contents of IFN-γ in the cultured supernatant were significantly lower than those of rBCG-Sj26GST vaccine group (P<0. 001), but were significantly increased as compared with that in thecontrol group (P<0.01). It was indicated that both vaccines could enhance the immune response ofthe mice, but rMS-Sj26GST vaccine had stronger immunogenicity than rBCG-Sj26GST vaccine.

  4. Theoretical Delay Time Distributions

    CERN Document Server

    Nelemans, Gijs; Bours, Madelon

    2012-01-01

    We briefly discuss the method of population synthesis to calculate theoretical delay time distributions of type Ia supernova progenitors. We also compare the results of the different research groups and conclude that although one of the main differences in the results for single degenerate progenitors is the retention efficiency with which accreted hydrogen is added to the white dwarf core, this cannot explain all the differences.

  5. Theoretical Delay Time Distributions

    Science.gov (United States)

    Nelemans, Gijs; Toonen, Silvia; Bours, Madelon

    2013-01-01

    We briefly discuss the method of population synthesis to calculate theoretical delay time distributions of Type Ia supernova progenitors. We also compare the results of different research groups and conclude that, although one of the main differences in the results for single degenerate progenitors is the retention efficiency with which accreted hydrogen is added to the white dwarf core, this alone cannot explain all the differences.

  6. Geometric Time Delay Interferometry

    OpenAIRE

    Vallisneri, Michele

    2005-01-01

    The space-based gravitational-wave observatory LISA, a NASA-ESA mission to be launched after 2012, will achieve its optimal sensitivity using Time Delay Interferometry (TDI), a LISA-specific technique needed to cancel the otherwise overwhelming laser noise in the inter-spacecraft phase measurements. The TDI observables of the Michelson and Sagnac types have been interpreted physically as the virtual measurements of a synthesized interferometer. In this paper, I present Geometric TDI, a new an...

  7. Time-Delay Interferometry

    OpenAIRE

    Dhurandhar Sanjeev V.; Tinto Massimo

    2005-01-01

    Equal-arm interferometric detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set overall performance. If, however, the two arms have different lengths (...

  8. Time-Delay Interferometry

    Directory of Open Access Journals (Sweden)

    Massimo Tinto

    2014-08-01

    Full Text Available Equal-arm detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set the overall performance. If, however, the two arms have different lengths (as will necessarily be the case with space-borne interferometers, the laser noise experiences different delays in the two arms and will hence not directly cancel at the detector. In order to solve this problem, a technique involving heterodyne interferometry with unequal arm lengths and independent phase-difference readouts has been proposed. It relies on properly time-shifting and linearly combining independent Doppler measurements, and for this reason it has been called time-delay interferometry (TDI. This article provides an overview of the theory, mathematical foundations, and experimental aspects associated with the implementation of TDI. Although emphasis on the application of TDI to the Laser Interferometer Space Antenna (LISA mission appears throughout this article, TDI can be incorporated into the design of any future space-based mission aiming to search for gravitational waves via interferometric measurements. We have purposely left out all theoretical aspects that data analysts will need to account for when analyzing the TDI data combinations.

  9. Delayed Speech or Language Development

    Science.gov (United States)

    ... to 2-Year-Old Delayed Speech or Language Development KidsHealth > For Parents > Delayed Speech or Language Development ... child is right on schedule. Normal Speech & Language Development It's important to discuss early speech and language ...

  10. Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy.

    Science.gov (United States)

    Ishii, Kazuo; Kurita-Taniguchi, Mitsue; Aoki, Mikio; Kimura, Toru; Kashiwazaki, Yasuo; Matsumoto, Misako; Seya, Tsukasa

    2005-05-15

    Adjuvants induce the expression of a number of genes in dendritic cells (DCs), which facilitate effective antigen-presentation and cytokine/chemokine liberation. It has been accepted that the toll-like receptor (TLR) family governs the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation by GeneChip analysis. We identified the genes supporting an efficient DC response and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation. BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally up-regulated some gene clusters including genes for inflammatory cytokines (TNF, IL1alpha, IL1beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.), cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B, BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up-regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2, IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS- or PGN-stimulation up-regulated CXCL5, MMP1, etc. We discussed their properties in association with TLRs and recently discovered TLR adapters.

  11. HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

    Directory of Open Access Journals (Sweden)

    Tsungai Ivai Jongwe

    Full Text Available Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA vaccines expressing HIV-1C mosaic Gag (GagM were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C.

  12. The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

    Directory of Open Access Journals (Sweden)

    Kiss Tamas

    2010-06-01

    Full Text Available Abstract Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG is effective in non-muscle-invasive bladder cancer (BC, adverse events (AEs are considerable. Monocyte-derived activated killer cells (MAK are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM® to BCG in patients after transurethral resection (TURB of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM. Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint and prophylactic effects (secondary endpoint were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE, respectively (p Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

  13. Polyclonal activation of naïve T cells by urease deficient-recombinant BCG that produced protein complex composed of heat shock protein 70, CysO and major membrane protein-II

    OpenAIRE

    Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Mukai, Tetsu; Makino, Masahiko

    2014-01-01

    Background Mycobacterium bovis bacillus Calmette-Guérin (BCG) is known to be only partially effective in inhibiting M. tuberculosis (MTB) multiplication in human. A new recombinant (r) urease-deficient BCG (BCG-dHCM) that secretes protein composed of heat shock protein (HSP)70, MTB-derived CysO and major membrane protein (MMP)-II was produced for the efficient production of interferon gamma (IFN-γ) which is an essential element for mycobacteriocidal action and inhibition of neutrophil accumul...

  14. Nanobiotechnologic approach to a promising vaccine prototype for immunisation against leishmaniasis: a fast and effective method to incorporate GPI-anchored proteins of Leishmania amazonensis into liposomes.

    Science.gov (United States)

    Colhone, Marcelle Carolina; Silva-Jardim, Izaltina; Stabeli, Rodrigo Guerino; Ciancaglini, Pietro

    2015-01-01

    Liposomes are known to be a potent adjuvant for a wide range of antigens, as well as appropriate antigen carriers for antibody generation response in vivo. In addition, liposomes are effective vehicles for peptides and proteins, thus enhancing their immunogenicity. Considering these properties of liposomes and the antigenicity of the Leishmania membrane proteins, we evaluated if liposomes carrying glycosylphosphatidylinositol (GPI)-anchored proteins of Leishmania amazonensis promastigotes could induce protective immunity in BALB/c mice. To assay protective immunity, BALB/c mice were intraperitoneally injected with liposomes, GPI-protein extract (EPSGPI) as well as with the proteoliposomes carrying GPI-proteins. Mice inoculated with EPSGPI and total protein present in constitutive proteoliposomes displayed a post-infection protection of about 70% and 90%, respectively. The liposomes are able to work as adjuvant in the EPSGPI protection. These systems seem to be a promising vaccine prototype for immunisation against leishmaniasis.

  15. Molecular typing of isolates obtained from aborted foetuses in Brucella-free Holstein dairy cattle herd after immunisation with Brucella abortus RB51 vaccine in Egypt.

    Science.gov (United States)

    Wareth, Gamal; Melzer, Falk; Böttcher, Denny; El-Diasty, Mohamed; El-Beskawy, Mohamed; Rasheed, Nesma; Schmoock, Gernot; Roesler, Uwe; Sprague, Lisa D; Neubauer, Heinrich

    2016-12-01

    Bovine brucellosis is endemic in Egypt in spite of application of surveillance and control measures. An increase of abortions was reported in a Holstein dairy cattle herd with 600 animals in Damietta governorate in Egypt after immunisation with Brucella (B.) abortus RB51 vaccine. Twenty one (10.6%) of 197 vaccinated cows aborted after 3 months. All aborted cows had been tested seronegative for brucellosis in the past 3 years. B. abortus was isolated from four foetuses. Conventional biochemical and bacteriological identification and polymerase chain reaction (PCR) confirmed two B. abortus biovar (bv.) 1 smooth and two B. abortus rough strains. None of the B. abortus isolates were identified as RB51. Genotyping analysis by multiple locus of variable number tandem repeats analysis based on 16 markers (MLVA-16) revealed two different profiles with low genetic diversity. B. abortus bv1 was introduced in the herd and caused abortions.

  16. Avaliação da resposta inflamatória hematológica em cascavéis (Crotalus durissus Linnaeus, 1758 inoculadas com BCG Assessment of blood inflammatory response in BCG stimulated rattlesnakes (Crotalus durissus Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Wellington Bandeira da Silva

    2009-12-01

    Full Text Available A criação de serpentes peçonhentas em cativeiro para produção de soros antipeçonhas possui crescente importância para a saúde pública devido ao aumento do número de notificações de acidentes ofídicos a cada ano no Brasil. Iniciado no século XX, ainda hoje essa atividade apresenta alguns desafios como a instalação de doenças no plantel. O hemograma é um exame de triagem clínica que auxilia no diagnóstico de diversas moléstias que acometem diferentes espécies de animais, no entanto ainda pouco estudado em serpentes. A caracterização das alterações hematológicas em cascavéis inoculadas experimentalmente com BCG pode servir de base na utilização deste exame no auxílio ao diagnóstico de infecções bacterianas na espécie. Dessa forma, foram realizados exames hematológicos em 10 serpentes da espécie Crotalus durissus pertencentes ao plantel da Divisão de Herpetologia do Instituto Vital Brazil. Os animais foram divididos em dois grupos (Grupos 1 e 2, homogêneos entre si em relação ao peso e proporção sexual. Os dois grupos foram inoculados com BCG e submetidos à coleta de sangue antes da inoculação e em três momentos pós-inoculação (3º, 5º, e 7º dias para o Grupo 1 e 11º, 17º e 21º dias para o Grupo 2. O hemograma foi realizado por método semidireto pela utilização de líquido de Natt e Herrick e as lâminas foram coradas pelo Giemsa. Observou-se anemia discreta, com redução dos valores de concentração de hemoglobina corpuscular média e da hemoglobina globular média no Grupo 1 que foi relacionada à doença inflamatória. A trombocitopenia observada no Grupo 2 sugeriu a atuação deste tipo celular em processos inflamatórios. Um único animal do Grupo 1 apresentou granulocitose e alguns animais apresentaram discreta azurofilia. Observaram-se alterações morfológicas nos leucócitos. Os granulócitos apresentaram granulações grosseiras e os azurófilos apresentaram aumento de tamanho e

  17. Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases.

    Science.gov (United States)

    Matyszak, M K; Perry, V H

    1996-09-01

    We have studied the effect of an inhibitor of matrix metalloproleinases, BB-1101, on a delayed-type hypersensitivity (DTH) response in the CNS. We used a recently described model in which heat-killed bacillus Calmette-Guérin (BCG) sequestered behind the blood-brain barrier (BBB) is targeted by a T-cell mediated response after subcutaneous injection of BCG (Matyszak and Perry, 1995). The DTH lesions are characterised by breakdown of the BBB, macrophage and lymphocyte infiltration and tissue damage including myelin loss. Treatment with BB-1101, which is not only a potent inhibitor of matrix metalloproteinases but also strongly inhibits TNF-alpha release, dramatically attenuated the CNS lesions. Breakdown of the BBB and the recruitment of T-cells into the site of the lesion were significantly reduced. There were many fewer inflammatory macrophages in DTH lesions than in comparable lesions from untreated animals. There was also significantly less myelin damage (assessed by staining with anti-MBP antibody). The DTH response in animals treated with dexamethasone was also reduced, but to a lesser degree. No significant effect was seen after administration of pentoxifylline, a phosphodiesterase inhibitor with effects including the inhibition of TNF-alpha production. Our results suggest that inhibitors of matrix metalloproteinases may be of considerable therapeutic benefit in neuroinflammatory diseases.

  18. Strategies for the transfusion of subjects with complex red cell immunisation: the Bank of rare blood donors of the Region of Lombardy

    Science.gov (United States)

    Morelati, Fernanda; Arnaboldi, Piera; Barocci, Fiorella; Bodini, Umberto; Boiani, Elisa; Bresciani, Susanna; Cambiè, Giuseppe; Cazzaniga, Giovanni; Cocco, Ernesto; Copeta, Alessandro; Crotti, Massimo; D’Agostino, Francesco; D’Agostino, Marco; Focchiatti, Valeria; Fonti, Elena; Galassi, Luigi; Gazzola, Giambattista; Gelpi, Luigi; Greppi, Noemi; Inghilleri, Giovanni Battista; Isernia, Paola; Manera, Maria Cristina; Marini, Mirella; Monti, Rosalia; Morales, Rino; Moroni, Gianalessandro; Morra, Enrica; Pau, Maria Paola; Paccapelo, Cinzia; Pagliaro, Pasqualepaolo; Prati, Daniele; Revelli, Nicoletta; Rinaldini, Claudia; Rossi, Davide; Rossi, Fabio; Salvaneschi, Laura; Sciariada, Luca; Sergiacomo, Pierluigi; Tiburzi, Alessandra; Trotti, Roberta; Turdo, Rosalia; Velati, Claudio; Villa, Maria Antonietta; Vismara, Giuseppina; Vitali, Elisabetta; Marconi, Maurizio

    2007-01-01

    Introduction Selecting units of rare blood for transfusion to patients with complex immunisation is one of the most critical processes of a Transfusion Centre. In January 2005 the ‘Rare Blood Components Bank – Reference Centre of the Region of Lombardy’ w as established with the following goals: 1) identifying regional rare blood donors; 2) creating a regional registry of rare donors; 3) organising a regional bank of liquid and frozen rare blood units; 4) setting up a regional Immunohaematology Reference Laboratory (IRL) to type donors and resolve complex cases. Methods The key elements in establishing the Bank were periodic meetings organised by the directors and representatives of the regional Departments of Transfusion Medicine and Haematology (DTMH) and the institution of three working groups (informatics, regulations, finance). Results The regional IRL was set up, the relevant operating procedures were distributed region-wide, software features were defined and later validated upon activation, and the funds assigned were allocated to various cost items. The number and characteristics of the donors to be typed were identified and 14 regional DTMHs started to send samples. Overall, 20,714 donors were typed, for a total of 258,003 typings, and 2,880 rare donors were identified. Of these, 97% were rare donors because of combinations of antigens (2,139 negative for the S antigen and 659 negative for the s antigen) and 3% (n=82) because they were negative for high-frequency antigens. In the first 2 years of activity, the IRL carried out investigations of 140 complex cases referred from other Centres and distributed 2,024 units with rare phenotypes to 142 patients. Conclusions The main goal achieved in the first 24 months from the start of the project was to set up a regional network able to meet the transfusion needs of patients with complex immunisation. PMID:19204778

  19. Delay Choice vs. Delay Maintenance: Different Measures of Delayed Gratification in Capuchin Monkeys (Cebus apella)

    Science.gov (United States)

    Addessi, Elsa; Paglieri, Fabio; Beran, Michael J.; Evans, Theodore A.; Macchitella, Luigi; De Petrillo, Francesca; Focaroli, Valentina

    2013-01-01

    Delaying gratification involves two components: (i) delay choice (selecting a delayed reward over an immediate one), and (ii) delay maintenance (sustaining the decision to delay gratification even if the immediate reward is available during the delay). In primates, two tasks most commonly have explored these components, the Intertemporal choice task and the Accumulation task. It is unclear whether these tasks provide equivalent measures of delay of gratification. Here, we compared the performance of the same capuchin monkeys, belonging to two study populations, between these tasks. We found only limited evidence of a significant correlation in performance. Consequently, in contrast to what is often assumed, our data provide only partial support to the hypothesis that these tasks provide equivalent measures of delay of gratification. PMID:23544770

  20. Compostos indutores e genes regulando a expressão da bomba de efluxo Tap em Mycobacterium bovis BCG

    OpenAIRE

    Felix, Carolina Rodrigues

    2013-01-01

    Proteínas transportadoras relacionada ao efluxo de drogas desempenham um papel importante não só na aquisição de fenótipos resistentes aos fármacos, mas também na virulência de M. tuberculosis. O principal objetivo deste estudo foi analisar a regulação do gene Rv1258c codificador da proteína Tap considerando a expressão dos genes Rv1255c e Rv1257c. RNA foi extraído a partir de culturas de M. bovis BCG superexpressando Rv1255c e Rv1257c, bem como de uma cepa controle contendo o vector pVV16 re...

  1. Infección diseminada por BCG en la Región de Los Lagos, Chile: Reporte de cinco casos clínicos Disseminated infection by BCG in Región de Los Lagos, Chile: Five cases report

    Directory of Open Access Journals (Sweden)

    ALEXIS STRICKLER P

    2009-01-01

    Full Text Available El bacilo Calmette-Guérin (BCG, es la cepa atenuada de Mycobacterium bovis utilizada en países en vías de desarrollo para la prevención de formas graves de tuberculosis. La vacuna BCG neonatal se administra en países con alta prevalencia de la enfermedad. La mayoría de los vacunados no presenta reacciones adversas, algunos evidencian reacciones secundarias a una inmunidad alterada del huésped. Dichas reacciones varían desde una simple adenomegalia ipsilateral a la inoculación de BCG, hasta una infección diseminada, a menudo mortal. La infección diseminada se ha descrito en pacientes inmuno deficientes secundarios, primarios y en pacientes con defectos genéticos del eje interleuquina 12-23 (IL12/23-interferón gama (IFN-γ denominados "Síndrome de predisposición mendeliana a infecciones micobacterianas" (PMIM. Describimos cinco pacientes con infección por M. bovis-BCG diagnosticados entre 1995-2008, en el Hospital Base de Puerto Montt, Región de Los Lagos, Chile que cumplen con los criterios del PMIM.The bacillus Calmette-Guérin (BCG is the attenuated strain of Mycobacterium bovis used in developing countries for preventing serious forms of tuberculosis. The neonatal BCG vaccine is applied in countries with high prevalence of tuberculosis. Most of the vaccinated individuáis develop no adverse reactions; although, some subjects show side effects due to a host altered immunity. These reactions range from a simple adenomegaly in the same side of BCG vaccine inoculation, to a spread infection, often fatal. A regional or systemic spread has been described in patients with secondary or primary immunodeficiencies and partial or total genetic defects of interleukin IL-12/23 and IFN-γ called as a whole "Mendelian susceptibility to mycobacterial infections" (MSMD. We describe five patients infected with M. bovis BCG-diagnosed between 1995-2008, at the base hospital in the city of Puerto Montt, Región de Los Lagos, Chile. These patients

  2. [Commemorative lecture of receiving Imamura Memorial Prize. II. Mode of action of oligonucleotide fraction extracted from Mycobacterium bovis BCG].

    Science.gov (United States)

    Yamamoto, S

    1994-09-01

    A fraction extracted from Mycobacterium bovis BCG was found to exhibit strong antitumor activity. This fraction, which was designated MY-1, caused some animal tumors to regress and/or prevent metastasis very effectively. MY-1 after digestion with DNase had almost completely reduced activity, while MY-1 digested with RNase did not. MY-1 also augmented natural killer (NK) cell activity of mouse spleen cells in vitro, and produced factors which showed anti-viral activity and rendered macrophages cytotoxic towards tumor cells. The function of the factor to activate macrophages was destroyed by treatment with anti-interferon (IFN)-gamma antibody, while the anti-viral activity was destroyed by treatment with anti-INF alpha/beta antibody. The oligonucleotides contained in MY-1 distributed in a broad range of molecular size, and peaked at 45 nucleotides. We synthesized 13 kinds of 45-mer nucleotides with sequence present in the known cDNA encoding various BCG proteins. Six out of these oligonucleotides, which contained one or more hexameric palindromic structures, showed strong antitumor activity, while the other without palindrome did not. These active oligonucleotides possessed the capability to induce IFN and to augment NK cell activity of mouse spleen cells by coincubation in vitro. When a portion of the sequence of the inactive oligonucleotides was substituted with either palindromic sequence of GACGTC, AGCGCT or AACGTT, the oligonucleotide acquired the ability to augment NK activity. In contrast, the oligonucleotides substituted with another palindromic sequence such as ACCGGT was without effect. Furthermore, exchange of two neighboring mononucleotides within, but not outside, the active palindromic sequence destroyed the ability of the oligonucleotide to augment NK activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Delaying information search

    Directory of Open Access Journals (Sweden)

    Yaniv Shani

    2012-11-01

    Full Text Available In three studies, we examined factors that may temporarily attenuate information search. People are generally curious and dislike uncertainty, which typically encourages them to look for relevant information. Despite these strong forces that promote information search, people sometimes deliberately delay obtaining valuable information. We find they may do so when they are concerned that the information might interfere with future pleasurable activities. Interestingly, the decision to search or to postpone searching for information is influenced not only by the value and importance of the information itself but also by well-being maintenance goals related to possible detrimental effects that negative knowledge may have on unrelated future plans.

  4. BCG Infection to Human B Cells Induce Cell Apoptosis%卡介苗感染人B细胞诱导细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    朱旗; 冯国栋; 杨毅宁; 赵青; 王文菁; 张敏; 刘扬; 赵钢

    2015-01-01

    目的 探究卡介苗( BCG)是否能感染人B细胞及观察感染后对细胞的影响. 方法 人B细胞系Raji细胞与BCG共培养, 4、12和24h后分别用共聚焦及透射电镜观察Raji细胞对BCG的结合和摄取情况,用CCK-8法检测细胞毒性,流式An-nexin Ⅴ-PI双标法检测细胞凋亡和坏死情况. 结果 培养4、12和24h后,感染了BCG的细胞比例分别为12. 4%±2. 0%, 23. 8%±5. 1%, 25. 2%±4. 8%.BCG感染可引起细胞毒性,4h后Raji细胞存活率为75. 5%±8. 8%,12h后细胞存活率降至51. 0%± 5. 3%,24h后细胞存活率仅为21. 6%±4. 2%,而感染灭活BCG的细胞存活率均在95%以上. 进一步用流式检测凋亡坏死发现,与未感染细胞相比,Raji细胞感染BCG后凋亡,坏死均有所增加,以凋亡增加为主. 结论 BCG可以感染人B细胞并诱导细胞凋亡.%Objective To explore whether Bacillus Calmette-Guérin ( BCG) can infect human B cells and observe the effects of the infection on B cells. Methods Human B cell line Raji cells were incubated with BCG. After incubation for 4h, 12h and 24h, the direct interaction of Raji cells with BCG was observed under confocal microscopy and transmission electronic microscopy. Cytotoxity was detected by cell counting kit (CCK-8). Cell apoptosis and necrosis were assayed by flow cytometry. Results After 4h, 12h and 24h of incuba-tion, the percentage of Raji cells that were infected by BCG was 12. 4%±2. 0%, 23. 8%±5. 1%, 25. 2%±4. 8%, respectively. Live BCG infection induced cytotoxicity. The cell survival rates at 4h, 12h, 24h were 75. 5%±8. 8%, 51. 0%±5. 3%, 21. 6%±4. 2% re-spectively, while the cells infected with inactivated BCG showed a high survival rate of 95% at any time. Further analysis by flow cytome-try showed that cell apoptosis and necrosis, predominantly cell apoptosis of Raji cells were increased by BCG infection. Conclusion BCG can infect human B cells and induce cell apoptosis.

  5. Epidemiology of delayed ejaculation.

    Science.gov (United States)

    Di Sante, Stefania; Mollaioli, Daniele; Gravina, Giovanni Luca; Ciocca, Giacomo; Limoncin, Erika; Carosa, Eleonora; Lenzi, Andrea; Jannini, Emmanuele A

    2016-08-01

    A large body of literature on diminished ejaculatory disorders has been generated without the use of a clear diagnostic definition. Many studies have not distinguished between the orgasm and ejaculation disorders leading to doubtful results. Delayed ejaculation (DE) is one of the diminished ejaculatory disorders, which range from varying delays in ejaculatory latency to a complete inability to ejaculate. The present review is aimed at providing a comprehensive overview of the current knowledge on the definition and epidemiology of diminished ejaculatory disorders. We focus on the acquired diseases, such as benign prostatic hyperplasia (BPH) and specific drug regimens that may cause an iatrogenic form of ejaculatory disorder. In addition, the impact of aging is discussed since the prevalence of DE appears to be moderately but positively related to age. Finally, we also focus on the importance of the hormonal milieu on male ejaculation. To date, evidence on the endocrine control of ejaculation is derived from small clinical trials, but the evidence suggests that hormones modulate the ejaculatory process by altering its overall latency.

  6. Pseudotumoral delayed cerebral radionecrosis

    Energy Technology Data Exchange (ETDEWEB)

    Ciaudo-Lacroix, C.; Lapresle, J. (Centre Hospitalier de Bicetre, 94 - Le Kremlin-Bicetre (France))

    1985-01-01

    A 60 year-old woman with a scalp epithelioma underwent radiotherapy, the dose being 57 Gray. A first epileptic seizure occurred twenty months later. Neurological examination revealed signs of left hemisphere involvement. ..gamma..EG, angiography, CT scans, demonstrated a pseudotumoral avascular process. On account of the localisation, the patient being right-handed, no surgical procedure was performed. In spite of corticotherapy and anticonvulsive treatment, seizures recurred and neurological signs slowly progressed. The patient died, 22 months after the first seizure, of an associated disseminated carcinoma with cachexia. Neuropathological examination showed a massive lesion presenting all the features of delayed radionecrosis in the left hemisphere: situated mainly in the white matter; numerous vascular abnormalities; wide-spread demyelination; disappearance of oligoglial cells. The Authors recall the clinical and anatomical aspects of this condition for which the only successful treatment is surgical removal when location and size of the lesion permit. Finally, the mechanisms which have been proposed to explain this delayed cerebral radionecrosis are discussed.

  7. Stability and delay sensitivity of neutral fractional-delay systems

    Science.gov (United States)

    Xu, Qi; Shi, Min; Wang, Zaihua

    2016-08-01

    This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

  8. Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons

    Directory of Open Access Journals (Sweden)

    Meywald-Walter K

    2006-05-01

    Full Text Available Abstract Background BCG-vaccination can confound tuberculin skin test (TST reactions in the diagnosis of latent tuberculosis infection. Methods We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON®-TB-Gold In Tube; QFT-G during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany. Results During a 6-month period, 309 contacts (mean age 28.5 ± 10.5 years from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8% had received BCG vaccination and 84 (27.2% had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000. For the TST, the positive response rate was 44.3% (137/309, whilst only 31 (10% showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (κ = 0.2, with 95% CI 0.14.-0.23, and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7–52.5. In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (κ = 0.58, with 95% CI 0.4–0.68, increasing to 0.68 (95% CI 0.46–0.81, if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany. Conclusion The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection.

  9. Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG Determining the risk of tuberculosis infection in BCG-vaccinated populations

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1992-04-01

    Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.The revaccination of schoolchildren can restore the residual allergy induced by vaccination in the first years of life but can not modify the allergy resulting from a

  10. Immunization with Bacillus Calmette-Guérin (BCG) alleviates neuroinflammation and cognitive deficits in APP/PS1 mice via the recruitment of inflammation-resolving monocytes to the brain.

    Science.gov (United States)

    Zuo, Zejie; Qi, Fangfang; Yang, Junhua; Wang, Xiao; Wu, Yingying; Wen, Yaru; Yuan, Qunfang; Zou, Juntao; Guo, Kaihua; Yao, Zhi Bin

    2017-05-01

    The immune system plays a crucial role in the progression of Alzheimer's disease (AD). Recently, immune-dependent cascade induced by systemic immune activation has been verified to play a beneficial role in AD mouse models. Here, we tested whether Bacillus Calmette-Guérin (BCG) immunization alters AD pathology and cognitive dysfunction in APP/PS1 AD mouse model, and with 4Aβ1-15 vaccination as positive control. It was found that BCG treatment reversed the cognitive decline to the extent observed in 4Aβ1-15 group, but did not reduce the β-amyloid (Aβ) burden in the brain. Then, we demonstrated the enhanced recruitment of inflammation-resolving monocytes across the choroid plexus and perivascular spaces to cerebral sites of plaque pathology in APP/PS1 mice immunized with BCG. Furthermore, elevated splenocyte Foxp3(+) regulatory T cell levels in the control APP/PS1 mice were down-regulated back to the wild-type (WT) levels by BCG treatment but not 4Aβ1-15 vaccination. In addition, BCG treatment induced the production of more circulating interferon (IFN)-γ than the controls and 4Aβ1-15 vaccination. Though the similar reductions in brain levels of pro-inflammatory cytokines were observed in the BCG and 4Aβ1-15 groups compared to the controls, only BCG had the great effect in upregulating cerebral anti-inflammatory cytokine levels as well as elevating the expression of neurotrophic factors in the brain of APP/PS1 mice. Thus, it is suggested that BCG exerts a beneficial immunomodulatory effect in APP/PS1 mice through mitigation of systemic immune suppression, induction of IFN-γ response and alleviation of the neuroinflammatory response.

  11. Assessment of an oral Mycobacterium bovis BCG vaccine and an inactivated M. bovis preparation for wild boar in terms of adverse reactions, vaccine strain survival, and uptake by nontarget species.

    Science.gov (United States)

    Beltrán-Beck, Beatriz; Romero, Beatriz; Sevilla, Iker A; Barasona, Jose A; Garrido, Joseba M; González-Barrio, David; Díez-Delgado, Iratxe; Minguijón, Esmeralda; Casal, Carmen; Vicente, Joaquín; Gortázar, Christian; Aranaz, Alicia

    2014-01-01

    Wildlife vaccination is increasingly being considered as an option for tuberculosis control. We combined data from laboratory trials and an ongoing field trial to assess the risk of an oral Mycobacterium bovis BCG vaccine and a prototype heat-inactivated Mycobacterium bovis preparation for Eurasian wild boar (Sus scrofa). We studied adverse reactions, BCG survival, BCG excretion, and bait uptake by nontarget species. No adverse reactions were observed after administration of BCG (n = 27) or inactivated M. bovis (n = 21). BCG was not found at necropsy (175 to 300 days postvaccination [n = 27]). No BCG excretion was detected in fecal samples (n = 162) or in urine or nasal, oral, or fecal swab samples at 258 days postvaccination (n = 29). In the field, we found no evidence of loss of BCG viability in baits collected after 36 h (temperature range, 11°C to 41°C). Camera trapping showed that wild boar (39%) and birds (56%) were the most frequent visitors to bait stations (selective feeders). Wild boar activity patterns were nocturnal, while diurnal activities were recorded for all bird species. We found large proportions of chewed capsules (29%) (likely ingestion of the vaccine) and lost baits (39%) (presumably consumed), and the proportion of chewed capsules showed a positive correlation with the presence of wild boar. Both results suggest proper bait consumption (68%). These results indicate that BCG vaccination in wild boar is safe and that, while bait consumption by other species is possible, this can be minimized by using selective cages and strict timing of bait deployment.

  12. Synchronizing time delay systems using variable delay in coupling

    Energy Technology Data Exchange (ETDEWEB)

    Ambika, G., E-mail: g.ambika@iiserpune.ac.in [Indian Institute of Science Education and Research, Pune 411 021 (India); Amritkar, R.E., E-mail: amritkar@prl.res.in [Physical Research Laboratory, Ahmedabad 380 009 (India)

    2011-11-15

    Highlights: > Delay and anticipation in coupling function varies with system dynamics. > Delay or anticipation of the synchronized state is independent of system delay. > Stability analysis developed is quite general. > We demonstrate enhanced security in communication. > Generalized synchronization possible over a wide range of parameter mismatch. - Abstract: We present a mechanism for synchronizing time delay systems using one way coupling with a variable delay in coupling that is reset at finite intervals. We present the analysis of the error dynamics that helps to isolate regions of stability of the synchronized state in the parameter space of interest for single and multiple delays. We supplement this by numerical simulations in a standard time delay system like Mackey Glass system. This method has the advantage that it can be adjusted to be delay or anticipatory in synchronization with a time which is independent of the system delay. We demonstrate the use of this method in communication using the bi channel scheme. We show that since the synchronizing channel carries information from transmitter only at intervals of reset time, it is not susceptible to an easy reconstruction.

  13. A single dose of a DNA vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in Mycobacterium bovis BCG-primed mice.

    Science.gov (United States)

    Carlétti, Dyego; Morais da Fonseca, Denise; Gembre, Ana Flávia; Masson, Ana Paula; Weijenborg Campos, Lívia; Leite, Luciana C C; Rodrigues Pires, Andréa; Lannes-Vieira, Joseli; Lopes Silva, Célio; Bonato, Vânia Luiza Deperon; Horn, Cynthia

    2013-08-01

    Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

  14. Location Estimation using Delayed Measurements

    DEFF Research Database (Denmark)

    Bak, Martin; Larsen, Thomas Dall; Nørgård, Peter Magnus

    1998-01-01

    When combining data from various sensors it is vital to acknowledge possible measurement delays. Furthermore, the sensor fusion algorithm, often a Kalman filter, should be modified in order to handle the delay. The paper examines different possibilities for handling delays and applies a new techn...... technique to a sensor fusion system for estimating the location of an autonomous guided vehicle. The system fuses encoder and vision measurements in an extended Kalman filter. Results from experiments in a real environment are reported...

  15. Demographic determinants of delayed divorce.

    Science.gov (United States)

    Chan, L Y; Heaton, T B

    1989-01-01

    This study identifies factors that predict delayed divorce in the US. The findings show that factors which influence marital stability in general also correlate with delayed divorce in the same direction. Wife's age at marriage, age of the youngest child, wife's religion, region of residence, and metropolitan residence have substantial effects of delayed divorce, but the effects of race, parental divorce, premarital pregnancy, and socioeconomic status are small.

  16. On the Gravitomagnetic Time Delay

    OpenAIRE

    Ciufolini, I.; Kopeikin, S.; Mashhoon, B.; Ricci, F

    2002-01-01

    We study the gravitational time delay in ray propagation due to rotating masses in the linear approximation of general relativity. Simple expressions are given for the gravitomagnetic time delay that occurs when rays of radiation cross a slowly rotating shell and propagate in the field of a distant rotating source. Moreover, we calculate the local gravitational time delay in the Goedel universe. The observational consequences of these results in the case of weak gravitational lensing are disc...

  17. Time Delay of CGM Sensors

    Science.gov (United States)

    Schmelzeisen-Redeker, Günther; Schoemaker, Michael; Kirchsteiger, Harald; Freckmann, Guido; Heinemann, Lutz; del Re, Luigi

    2015-01-01

    Background: Continuous glucose monitoring (CGM) is a powerful tool to support the optimization of glucose control of patients with diabetes. However, CGM systems measure glucose in interstitial fluid but not in blood. Rapid changes in one compartment are not accompanied by similar changes in the other, but follow with some delay. Such time delays hamper detection of, for example, hypoglycemic events. Our aim is to discuss the causes and extent of time delays and approaches to compensate for these. Methods: CGM data were obtained in a clinical study with 37 patients with a prototype glucose sensor. The study was divided into 5 phases over 2 years. In all, 8 patients participated in 2 phases separated by 8 months. A total number of 108 CGM data sets including raw signals were used for data analysis and were processed by statistical methods to obtain estimates of the time delay. Results: Overall mean (SD) time delay of the raw signals with respect to blood glucose was 9.5 (3.7) min, median was 9 min (interquartile range 4 min). Analysis of time delays observed in the same patients separated by 8 months suggests a patient dependent delay. No significant correlation was observed between delay and anamnestic or anthropometric data. The use of a prediction algorithm reduced the delay by 4 minutes on average. Conclusions: Prediction algorithms should be used to provide real-time CGM readings more consistent with simultaneous measurements by SMBG. Patient specificity may play an important role in improving prediction quality. PMID:26243773

  18. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    period of delay can potentially be attributed to several events falling within both parties' spheres of responsibility, commonly termed concurrent delay, is rarely regulated in construction contracts in spite of its common occurrence. This book analyses both the theoretical foundations and the practical......Delay is one of the issues most frequently encountered in today’s construction industry; it causes significant economic damage to all parties involved. Construction contracts, standard and bespoke, almost invariably consider delay from a perspective of single liability. If the event causing...

  19. Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development: Results from the Danish Calmette Study - A Randomised Clinical Trial

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie;

    2016-01-01

    MEASURES: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age Developmental assessment was available for 3453/4262 (81%). RESULTS......OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals...... was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....

  20. WT1 peptide vaccination combined with BCG-CWS is more efficient for tumor eradication than WT1 peptide vaccination alone.

    Science.gov (United States)

    Nakajima, Hiroko; Kawasaki, Kotomi; Oka, Yoshihiro; Tsuboi, Akihiro; Kawakami, Manabu; Ikegame, Kazuhiro; Hoshida, Yoshihiko; Fujiki, Fumihiro; Nakano, Akiko; Masuda, Tomoki; Wu, Fei; Taniguchi, Yuki; Yoshihara, Satoshi; Elisseeva, Olga A; Oji, Yusuke; Ogawa, Hiroyasu; Azuma, Ichiro; Kawase, Ichiro; Aozasa, Katsuyuki; Sugiyama, Haruo

    2004-07-01

    A Wilms' tumor gene WT1 is expressed at high levels not only in most types of leukemia but also in various types of solid tumors, including lung and breast cancer. WT1 protein has been reported to serve as a target antigen for tumor-specific immunotherapy both in vitro in human systems and in vivo in murine models. We have shown that mice immunized with WT1 peptide or WT1 cDNA could reject a challenge from WT1-expressing tumor cells (a "prophylactic" model). However, it was not examined whether WT1 peptide vaccination had the potency to reject tumor cells in a "therapeutic" setting. In the present study, we demonstrated for the first time that WT1 peptide vaccination combined with Mycobacterium bovis bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) was more effective for eradication of WT1-expressing tumor cells that had been implanted into mice before vaccination (a "therapeutic" model) compared with WT1 peptide vaccination alone. An intradermal injection of BCG-CWS into mice, followed by that of WT1 peptide at the same site on the next day, generated WT1-specific cytotoxic T lymphocytes (CTLs) and led to rejection of WT1-expressing leukemia or lung cancer cells. These results showed that BCG-CWS, which was well known to enhance innate immunity, could enhance WT1-specific immune responses (acquired immunity) in combination with WT1 peptide vaccination. Therefore, WT1 peptide vaccination combined with BCG-CWS may be applied to cancer immunotherapy in clinical settings.

  1. Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Jensen, Kristoffer Jarlov; Aamand, Susanne Havn

    2015-01-01

    reaction (geometric mean ratio: 1.40 (1.20-1.63)) at 2 months. In response to secondary heterologous stimulation, monocytes primed with Slow growth batches induced higher IL-6 (p=0.03) and TNF-α responses (p=0.03) compared with Normal growth batches. CONCLUSION: The study indicates that variations...... in the production of BCG vaccine may influence important immunological effects of the vaccine. TRIAL REGISTRATION: clinicaltrials.gov (NCT00625482)....

  2. Boosting BCG-primed mice with chimeric DNA vaccine HG856A induces potent multifunctional T cell responses and enhanced protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Ji, Ping; Hu, Zhi-Dong; Kang, Han; Yuan, Qin; Ma, Hui; Wen, Han-Li; Wu, Juan; Li, Zhong-Ming; Lowrie, Douglas B; Fan, Xiao-Yong

    2016-02-01

    The tuberculosis pandemic continues to rampage despite widespread use of the current Bacillus Calmette-Guerin (BCG) vaccine. Because DNA vaccines can elicit effective antigen-specific immune responses, including potent T cell-mediated immunity, they are promising vehicles for antigen delivery. In a prime-boost approach, they can supplement the inadequate anti-TB immunological memory induced by BCG. Based on this, a chimeric DNA vaccine HG856A encoding Mycobacterium tuberculosis (M. tuberculosis) immunodominant antigen Ag85A plus two copies of ESAT-6 was constructed. Potent humoral immune responses, as well as therapeutic effects induced by this DNA vaccine, were observed previously in M. tuberculosis-infected mice. In this study, we further evaluated the antigen-specific T cell immune responses and showed that repeated immunization with HG856A gave modest protection against M. tuberculosis challenge infection and significantly boosted the immune protection primed by BCG vaccination. Enhanced protection was accompanied by increased multifunctional Th1 CD4(+) T cell responses, most notably by an elevated frequency of M. tuberculosis antigen-specific IL-2-producing CD4(+) T cells post-vaccination. These data confirm the potential of chimeric DNA vaccine HG856A as an anti-TB vaccine candidate.

  3. Impact of the BCG vaccination policy on tuberculous meningitis in children under 6 years in metropolitan France between 2000 and 2011.

    Science.gov (United States)

    Van Bui, T; Lévy-Bruhl, D; Che, D; Antoine, D; Jarlier, V; Robert, J

    2015-03-19

    In France, Bacillus Calmette–Guérin (BCG) vaccination by multipuncture device was withdrawn in 2006. In 2007, universal mandatory BCG vaccination was replaced by vaccination of high-risk children. To evaluate the impact of these changes on tuberculous meningitis (TBM) epidemiology, data on culture-positive and culture-negative (or unknown microbiological result) TBM in ≤5 years olds were collected from 2000–2011. Ten culture-positive and 17 culture-negative TBM cases were identified, with an annual incidence rate ranging from 0.16 to 0.66 cases per 10 million inhabitants. The average annual numbers of TBM cases were 2.7 and 1.8 from 2000–2005 and 2006–2011, respectively. In Ile-de-France where all children are considered at risk, the overall incidence rates were 1.14 and 0.29 per million for the two periods. In other regions where only at-risk children are vaccinated since 2007, rates were 0.30 and 0.47, respectively. None of these differences were significant. Annual incidence rates for each one year age group cohort were comparable before and after changes. Childhood TBM remains rare in France. No increase in incidence was observed after changes in BCG vaccination strategy. Ongoing surveillance should be maintained, as a slight increase in TBM in the coming years remains possible, in the context of suboptimal vaccination coverage of high-risk children.

  4. Constraining the Scatter in the Mass-Richness Relation of maxBCG Clusters With Weak Lensing and X-ray Data

    Energy Technology Data Exchange (ETDEWEB)

    Rozo, Eduardo; /Ohio State U.; Rykoff, Eli S.; /UC, Santa Barbara; Evrard, August; /Michigan U.; Becker, Matthew R.; /Chicago U.; McKay, Timothy; /Michigan U.; Wechsler, Risa H.; /SLAC; Koester, Benjamin P.; /Chicago U. /KICP, Chicago; Hao, Jiangang; /Michigan U.; Hansen, Sarah; /Chicago U. /KICP, Chicago; Sheldon, Erin; /New York U.; Johnston, David; /Houston U.; Annis, James T.; /Fermilab; Frieman, Joshua A.; /Chicago U. /KICP, Chicago /Fermilab

    2009-08-03

    We measure the logarithmic scatter in mass at fixed richness for clusters in the maxBCG cluster catalog, an optically selected cluster sample drawn from SDSS imaging data. Our measurement is achieved by demanding consistency between available weak lensing and X-ray measurements of the maxBCG clusters, and the X-ray luminosity-mass relation inferred from the 400d X-ray cluster survey, a flux limited X-ray cluster survey. We find {sigma}{sub lnM|N{sub 200}} = 0.45{sub -0.18}{sup +0.20} (95%CL) at N{sub 200} {approx} 40, where N{sub 200} is the number of red sequence galaxies in a cluster. As a byproduct of our analysis, we also obtain a constraint on the correlation coefficient between lnL{sub X} and lnM at fixed richness, which is best expressed as a lower limit, r{sub L,M|N} {ge} 0.85 (95% CL). This is the first observational constraint placed on a correlation coefficient involving two different cluster mass tracers. We use our results to produce a state of the art estimate of the halo mass function at z = 0.23 - the median redshift of the maxBCG cluster sample - and find that it is consistent with the WMAP5 cosmology. Both the mass function data and its covariance matrix are presented.

  5. Dynamic observation of immune responses induced in mice by immunization with a recombinant BCG-TSOL18 vaccine of Taenia solium%猪带绦虫重组BCG-TSOL18疫苗诱导小鼠免疫应答的动态观察

    Institute of Scientific and Technical Information of China (English)

    杨凤娇; 江楠; 周泠; 刘晖; 王灵军; 周必英

    2015-01-01

    Objective To dynamically observe humoral and cellular immune responses induced in mice by immunization with a recombinant BCG-TSOL18 vaccine of Taenia solium.Methods Totally 80 Kunming mice were divided into 4 groups by using random number table according to body mass, 20 mice in each group: rBCG-TSOL18 intraperitoneal injection group [mice were vaccinated with 5 × 106 colony forming units (CFU) recombinant BCG-TSOL18 vaccine of Taenia solium through intraperitoneal injection], rBCG-TSOL18 intragastric administration group(mice were vaccinated with 4 × 108 CFU recombinant BCG-TSOL18 vaccine of Taenia solium through intragastric administration), BCG control (mice were vaccinated with 5 × 106 CFU BCG through intraperitoneal injection), PBS control (mice were vaccinated with PBS through intraperitoneal injection).Zero, 2, 4, 6 and 8 weeks after immunization, eye blood was collected and serum w as separated.Levels of specific IgG and IgG2a were detected by enzyme linked immunosorbent assay (ELISA).Proliferation level of spleen lymphocytes was detected by CCK-8.Levels of interleukin-2 (IL-2) and IL-4 were determined by ELISA.Results The level of specific IgG in rBCG-TSOL18 intraperitoneal injection group and rBCG-TSOL18 intragastric administration group increased from 2 to 8 weeks, and reached the highest level by the 6th week (0.310 ± 0.022, 0.356 ± 0.026).Compared with 0 week in the same group, BCG and PBS control group of the same time periods (0.054 ± 0.005, 0.057 ± 0.006, 0.093 ± 0.014, 0.085 ± 0.010), there were statistically significant differences (all P < 0.05).The level of specific IgG2a increased from 2 to 8 weeks, and reached the highest level by the 6th week (0.965 ± 0.031, 1.144 ± 0.049).Compared with 0 week in the same group, BCG and PBS control group of the same time periods (0.102 ± 0.014, 0.093 ± 0.012, 0.115 ± 0.012, 0.103 ± 0.013), there were statistically significant differences (all P < 0.05).The proliferation level of spleen

  6. Magnetic bearing optical delay line

    NARCIS (Netherlands)

    Dool, T.C. van den; Kamphues, F.G.; Fouss, B.; Henrioulle, K.; Hogenhuis, H.

    2004-01-01

    TNO TPD, in close cooperation with Micromega-Dynamics and Dutch Space, has developed an advanced Optical Delay Line (ODL) for use in PRIMA, GENIE and other ground based interferometers. The delay line design is modular and flexible, which makes scaling for other applications a relatively easy task.

  7. #FakeNobelDelayReasons

    CERN Multimedia

    2013-01-01

    Tuesday’s hour-long delay of the Nobel Prize in Physics announcement was (and still is) quite the cause for speculation. But on the Twittersphere, it was simply the catalyst for some fantastic puns, so-bad-they're-good physics jokes and other shenanigans. Here are some of our favourite #FakeNobelDelayReasons.    

  8. Imitation dynamics with time delay.

    Science.gov (United States)

    Wang, Shi-Chang; Yu, Jie-Ru; Kurokawa, Shun; Tao, Yi

    2017-02-28

    Based on the classic imitation dynamics (Hofbauer and Sigmund, 1998, Evolutionary Games and Population Dynamics, Cambridge University Press), the imitation dynamics with time delay is investigated, where the probability that an individual will imitate its opponent's own strategy is assumed to depend on the comparison between the past expected payoff of this individual's own strategy and the past expected payoff of its opponent's own strategy, i.e. there is a time delay effect. For the two-phenotype model, we show that if the system has an interior equilibrium and this interior equilibrium is stable when there is no time delay, then there must be a critical value of time delay such that the system tends to a stable periodic solution when the time delay is larger than the critical value. On the other hand, for three-phenotype (rock-scissors-paper) model, the numerical analysis shows that for the stable periodic solution induced by the time delay, the amplitude and the period will increase with the increase of the time delay. These results should help to understand the evolution of behavior based on the imitation dynamics with time delay.

  9. Calibrating for Ionospheric Phase Delays

    Science.gov (United States)

    Macdoran, P. F.

    1985-01-01

    Technique determines ionospheric phase delay on real-time universally applicable basis in terms of electrons per meter squared by coherently modulating two L-band carrier frequencies received from two Global Positioning System satelites. Two pseudorandom number sequences cross-correlated to derive delay time.

  10. Time-delay damping theory

    Institute of Scientific and Technical Information of China (English)

    洪峰

    2002-01-01

    In this paper, existing damping theories are briefly reviewed. On the basis of the existing damping theories, a new kind of damping theory, i.e., the time-delay damping theory, is developed. In the time-delay damping theory, the damping force is considered to be directly proportional to the increment of displacement. The response analysis of an SDOF time-delay damping system is carried out, and the methods for obtaining the solution for a time-delay damping system in the time domain as well as the frequency domain are given. The comparison between results from different damping theories shows that the time-delay damping theory is both reasonable and convenient.

  11. Asynchronous Bounded Expected Delay Networks

    CERN Document Server

    Bakhshi, Rena; Fokkink, Wan; Pang, Jun

    2010-01-01

    The commonly used asynchronous bounded delay (ABD) network models assume a fixed bound on message delay. We propose a probabilistic network model, called asynchronous bounded expected delay (ABE) model. Instead of a strict bound, the ABE model requires only a bound on the expected message delay. While the conditions of ABD networks restrict the set of possible executions, in ABE networks all asynchronous executions are possible, but executions with extremely long delays are less probable. In contrast to ABD networks, ABE networks cannot be synchronised efficiently. At the example of an election algorithm, we show that the minimal assumptions of ABE networks are sufficient for the development of efficient algorithms. For anonymous, unidirectional ABE rings of known size N we devise a probabilistic leader election algorithm having average message and time complexity O(N).

  12. Delayed radiation neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, T.; Miyamoto, K.; Beppu, H.; Hirose, K.; Yamada, K. (Tokyo Metropolitan Neurological Hospital (Japan))

    1981-07-01

    A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author).

  13. Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

    Science.gov (United States)

    Clark, Simon; Cross, Martin L; Smith, Alan; Court, Pinar; Vipond, Julia; Nadian, Allan; Hewinson, R Glyn; Batchelor, Hannah K; Perrie, Yvonne; Williams, Ann; Aldwell, Frank E; Chambers, Mark A

    2008-10-29

    Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery

  14. A derivation of masses and total luminosities of galaxy groups and clusters in the maxBCG catalogue

    CERN Document Server

    Proctor, Robert N; Azanha, Luiz; Dupke, Renato; Overzier, Roderik

    2015-01-01

    We report the results of a multi-waveband analysis of the masses and luminosities of $\\sim$600 galaxy groups and clusters identified in the maxBCG catalogue. These data are intended to form the basis of future work on the formation of the "$m_{12}$ gap" in galaxy groups and clusters. We use SDSS spectroscopy and $g$, $r$ and $i$ band photometry to estimate galaxy group/cluster virial radii, masses and total luminosities. In order to establish the robustness of our results, we compare them with literature studies that utilize a variety of mass determinations techniques (dynamical, X-ray, weak lensing) and total luminosities estimated in the $B$, $r$, $i$, and $K$ wavebands. We also compare our results to predictions derived from the Millennium Simulation. We find that, once selection effects are properly accounted for, excellent agreement exists between our results and the literature with the exception of a single observational study. We also find that the Millennium Simulation does an excellent job of predict...

  15. Development of a low-dose fast-dissolving tablet formulation of Newcastle disease vaccine for low-cost backyard poultry immunisation.

    Science.gov (United States)

    Lal, M; Zhu, C; McClurkan, C; Koelle, D M; Miller, P; Afonso, C; Donadeu, M; Dungu, B; Chen, D

    2014-05-17

    The immunisation of backyard poultry is critical for maintaining healthy flocks to provide nutrition and income for low-resource farmers worldwide. A vaccine presentation for flocks of less than 50 birds could make it more affordable and accessible, increasing uptake and impact. Fast-dissolving tablets (FDT) of Newcastle disease virus (NDV) vaccine were produced by freeze drying the LaSota NDV strain combined with excipients into tablets containing a small number of doses and packaged in polymer blister sheets. The NDV-FDT vaccine maintained virus stability for more than six months at 4°C, based on plaque assay and egg infectivity dose data. Stability was further confirmed in a challenge study, where the tablet vaccine elicited a strong immune response and provided 100 per cent protection to vaccinated chickens infected with a virulent strain of NDV. The vaccine tablet can be diluted in water (no needle or syringe required) and administered either in drinking water or with a dropper via an intraocular and/or intransal route. Results indicate that FDTs containing a small number of doses are a feasible presentation for backyard poultry farmers. The compact packaging of the FDTs will also provide cost savings in storing and distributing the vaccine in the cold chain.

  16. Is primary prevention of childhood obesity by education at 13-month immunisations feasible and acceptable? Results from a general practice based pilot study.

    LENUS (Irish Health Repository)

    Doorley, E

    2015-01-01

    Abstract Prevalence of childhood overweight and obesity remains high in Ireland. In this study an intervention conducted within primary care was evaluated. This involved a structured discussion with parents at the 13 month immunisations with their general practitioner (GP), including measuring weight of the toddler and parental education regarding healthy nutrition and physical activity for their toddler. There was a telephone follow-up interview with parents three months later assessing change in toddler diet\\/lifestyle. Endpoints assessed included parents\\' reports of specific lifestyle parameters with regard to the toddler and parental assessment of the usefulness of the intervention. 39 toddlers were studied. Most lifestyle parameters had improved at follow up. Reported fruit and vegetable intake of more than 4 portions per day increased from 20.5% of toddlers at baseline 28.6% at follow up. The number of toddlers abstaining from unhealthy snacks increased from 15.4% to 21.4%. Television watching of more than 2 hours daily decreased from 12.8% to 0%. Supervised exercise of more than thirty minutes per day increased from 69.2% to 89.3%. The majority of parents reported at follow up that they found the intervention acceptable (100%, n = 28) and useful (79%, n = 22).

  17. Time Delay in Molecular Photoionization

    CERN Document Server

    Hockett, P; Villeneuve, D M; Corkum, P B

    2015-01-01

    Time-delays in the photoionization of molecules are investigated. As compared to atomic ionization, the time-delays expected from molecular ionization present a much richer phenomenon, with a strong spatial dependence due to the anisotropic nature of the molecular scattering potential. We investigate this from a scattering theory perspective, and make use of molecular photoionization calculations to examine this effect in representative homonuclear and hetronuclear diatomic molecules, nitrogen and carbon monoxide. We present energy and angle-resolved maps of the Wigner delay time for single-photon valence ionization, and discuss the possibilities for experimental measurements.

  18. Delays and networked control systems

    CERN Document Server

    Hetel, Laurentiu; Daafouz, Jamal; Johansson, Karl

    2016-01-01

    This edited monograph includes state-of-the-art contributions on continuous time dynamical networks with delays. The book is divided into four parts. The first part presents tools and methods for the analysis of time-delay systems with a particular attention on control problems of large scale or infinite-dimensional systems with delays. The second part of the book is dedicated to the use of time-delay models for the analysis and design of Networked Control Systems. The third part of the book focuses on the analysis and design of systems with asynchronous sampling intervals which occur in Networked Control Systems. The last part of the book exposes several contributions dealing with the design of cooperative control and observation laws for networked control systems. The target audience primarily comprises researchers and experts in the field of control theory, but the book may also be beneficial for graduate students. .

  19. Leibniz Dynamics with Time Delay

    OpenAIRE

    Albu, I. D.; Opris, D.

    2005-01-01

    In this paper we show that several dynamical systems with time delay can be described as vector fields associated to smooth functions via a bracket of Leibniz structure. Some examples illustrate the theoretical considerations.

  20. Language Delays in Toddlers: Information for Parents

    Science.gov (United States)

    ... Stages Listen Español Text Size Email Print Share Language Delays in Toddlers: Information for Parents Page Content ... situation or repeats scripts from TV Delays in language Delays in language are the most common types ...

  1. Systematics in delayed neutron yields

    Energy Technology Data Exchange (ETDEWEB)

    Ohsawa, Takaaki [Kinki Univ., Higashi-Osaka, Osaka (Japan). Atomic Energy Research Inst.

    1998-03-01

    An attempt was made to reproduce the systematic trend observed in the delayed neutron yields for actinides on the basis of the five-Gaussian representation of the fission yield together with available data sets for delayed neutron emission probability. It was found that systematic decrease in DNY for heavier actinides is mainly due to decrease of fission yields of precursors in the lighter side of the light fragment region. (author)

  2. Time Delay in Molecular Photoionization

    OpenAIRE

    Hockett, P.; Frumker, E.; Villeneuve, D M; Corkum, P. B.

    2015-01-01

    Time-delays in the photoionization of molecules are investigated. As compared to atomic ionization, the time-delays expected from molecular ionization present a much richer phenomenon, with a strong spatial dependence due to the anisotropic nature of the molecular scattering potential. We investigate this from a scattering theory perspective, and make use of molecular photoionization calculations to examine this effect in representative homonuclear and hetronuclear diatomic molecules, nitroge...

  3. Measuring information-transfer delays.

    Directory of Open Access Journals (Sweden)

    Michael Wibral

    Full Text Available In complex networks such as gene networks, traffic systems or brain circuits it is important to understand how long it takes for the different parts of the network to effectively influence one another. In the brain, for example, axonal delays between brain areas can amount to several tens of milliseconds, adding an intrinsic component to any timing-based processing of information. Inferring neural interaction delays is thus needed to interpret the information transfer revealed by any analysis of directed interactions across brain structures. However, a robust estimation of interaction delays from neural activity faces several challenges if modeling assumptions on interaction mechanisms are wrong or cannot be made. Here, we propose a robust estimator for neuronal interaction delays rooted in an information-theoretic framework, which allows a model-free exploration of interactions. In particular, we extend transfer entropy to account for delayed source-target interactions, while crucially retaining the conditioning on the embedded target state at the immediately previous time step. We prove that this particular extension is indeed guaranteed to identify interaction delays between two coupled systems and is the only relevant option in keeping with Wiener's principle of causality. We demonstrate the performance of our approach in detecting interaction delays on finite data by numerical simulations of stochastic and deterministic processes, as well as on local field potential recordings. We also show the ability of the extended transfer entropy to detect the presence of multiple delays, as well as feedback loops. While evaluated on neuroscience data, we expect the estimator to be useful in other fields dealing with network dynamics.

  4. Basin stability in delayed dynamics

    Science.gov (United States)

    Leng, Siyang; Lin, Wei; Kurths, Jürgen

    2016-02-01

    Basin stability (BS) is a universal concept for complex systems studies, which focuses on the volume of the basin of attraction instead of the traditional linearization-based approach. It has a lot of applications in real-world systems especially in dynamical systems with a phenomenon of multi-stability, which is even more ubiquitous in delayed dynamics such as the firing neurons, the climatological processes, and the power grids. Due to the infinite dimensional property of the space for the initial values, how to properly define the basin’s volume for delayed dynamics remains a fundamental problem. We propose here a technique which projects the infinite dimensional initial state space to a finite-dimensional Euclidean space by expanding the initial function along with different orthogonal or nonorthogonal basis. A generalized concept of basin’s volume in delayed dynamics and a highly practicable calculating algorithm with a cross-validation procedure are provided to numerically estimate the basin of attraction in delayed dynamics. We show potential applicabilities of this approach by applying it to study several representative systems of biological or/and physical significance, including the delayed Hopfield neuronal model with multistability and delayed complex networks with synchronization dynamics.

  5. Infeccão tuberculosa natural e o uso do BCG oral e intradérmico em escolares de Laranjal Paulista, SP, Brasil Tuberculosis infections and the use of oral and intradermic BCG in school children from Laranjal Paulista, S. Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Eurivaldo Sampaio de Almeida

    1973-09-01

    Full Text Available Foi pesquisado no 2.° semestre de 1969, o índice de infecção tuberculosa nos escolares de nível primário da sede municipal de Laranjal Paulista, SP, com faixa etária de 7 a 15 anos. Utilizou-se PPD RT23 com 2UT (0,04 mcg de acordo com a 2.ª recomendação do Serviço Nacional de Tuberculose, sendo encontrado nível de 8% de reatores fortes o que sugere necessidade de intensificação local do controle da tuberculose. Houve diferenças significativas a 5% quanto à cor e grupo etário, predominando nos "não brancos" e nos de 11 a 15 anos, o mesmo não ocorrendo, entretanto, quanto ao sexo. Os reatores e seus conviventes foram encaminhados ao Dispensário de Tuberculose. Foi também pesquisada a viragem tuberculínica pelo BCG oral e intradérmico, comparados com grupo controle, encontrando-se resultados significantes. O resultado verificado no grupo que tomou BCG por via intradérmica foi quase duas vezes maior que os observados no grupo de BCG oral. Não houve diferenças quanto ao sexo e grupo etário, mas o grupo "não branco" mostrou-se mais reativo. Não foram definidas estatisticamente as reações pós-vacinais e a expectativa populacional foi considerada dentro da esperada para atividades desse tipo.The rate of tuberculosis infections was studied in 92.1% of all the 7 to 15 years old school children from the District of Laranjal Paulista, Sp. Tests were made with PPd-RT23 with 2UP (0.04mcg, as recomended by the "Serviço Nacional de Tuberculose". Strong positive reactions (10 or more mm in diameter were obtained in 8% of the tested children, an indication of the necessity of improvement in the local efforts to control tuberculosis. Positive results were significantly (P 0,05 more frequent in non whites as well as in the 11 - 15 years old group; no significant differences were observed related to sex. Samples of PPd negatives received oral or intradermic BCG; positives PPd's atfer intradermic BCG were almost two times more

  6. Removal of BCG artifacts from EEG recordings inside the MR scanner: a comparison of methodological and validation-related aspects.

    Science.gov (United States)

    Vanderperren, Katrien; De Vos, Maarten; Ramautar, Jennifer R; Novitskiy, Nikolay; Mennes, Maarten; Assecondi, Sara; Vanrumste, Bart; Stiers, Peter; Van den Bergh, Bea R H; Wagemans, Johan; Lagae, Lieven; Sunaert, Stefan; Van Huffel, Sabine

    2010-04-15

    Multimodal approaches are of growing interest in the study of neural processes. To this end much attention has been paid to the integration of electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data because of their complementary properties. However, the simultaneous acquisition of both types of data causes serious artifacts in the EEG, with amplitudes that may be much larger than those of EEG signals themselves. The most challenging of these artifacts is the ballistocardiogram (BCG) artifact, caused by pulse-related electrode movements inside the magnetic field. Despite numerous efforts to find a suitable approach to remove this artifact, still a considerable discrepancy exists between current EEG-fMRI studies. This paper attempts to clarify several methodological issues regarding the different approaches with an extensive validation based on event-related potentials (ERPs). More specifically, Optimal Basis Set (OBS) and Independent Component Analysis (ICA) based methods were investigated. Their validation was not only performed with measures known from previous studies on the average ERPs, but most attention was focused on task-related measures, including their use on trial-to-trial information. These more detailed validation criteria enabled us to find a clearer distinction between the most widely used cleaning methods. Both OBS and ICA proved to be able to yield equally good results. However, ICA methods needed more parameter tuning, thereby making OBS more robust and easy to use. Moreover, applying OBS prior to ICA can optimize the data quality even more, but caution is recommended since the effect of the additional ICA step may be strongly subject-dependent.

  7. Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

    Science.gov (United States)

    Cross, Martin L; Henderson, Ray J; Lambeth, Matthew R; Buddle, Bryce M; Aldwell, Frank E

    2009-07-01

    Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oral-delivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km(2). Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10(8) BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife.

  8. Mycobacterium tuberculosis PPD-induced immune biomarkers measurable in vitro following BCG vaccination of UK adolescents by multiplex bead array and intracellular cytokine staining

    Directory of Open Access Journals (Sweden)

    Worth Andrew

    2010-07-01

    Full Text Available Abstract Background The vaccine efficacy reported following Mycobacterium bovis Bacillus Calmette Guerin (BCG administration to UK adolescents is 77% and defining the cellular immune response in this group can inform us as to the nature of effective immunity against tuberculosis. The aim of this study was to identify which cytokines and lymphocyte populations characterise the peripheral blood cellular immune response following BCG vaccination. Results Diluted blood from before and after vaccination was stimulated with Mycobacterium tuberculosis purified protein derivative for 6 days, after which soluble biomarkers in supernatants were assayed by multiplex bead array. Ten out of twenty biomarkers measured were significantly increased (p Mycobacterium tuberculosis purified protein derivative stimulation of PBMC samples from the 12 month group revealed that IFNγ expression was detectable in CD4 and CD8 T-cells and natural killer cells. Polyfunctional flow cytometry analysis demonstrated that cells expressing IFNγ alone formed the majority in each subpopulation of cells. Only in CD4 T-cells and NK cells were there a notable proportion of responding cells of a different phenotype and these were single positive, TNFα producers. No significant expression of the cytokines IL-2, IL-17 or IL-10 was seen in any population of cells. Conclusions The broad array of biomarker responses detected by multiplex bead array suggests that BCG vaccination is capable, in this setting, of inducing a complex immune phenotype. Although polyfunctional T-cells have been proposed to play a role in protective immunity, they were not present in vaccinated adolescents who, based on earlier epidemiological studies, should have developed protection against pulmonary tuberculosis. This may be due to the later sampling time point available for testing or on the kinetics of the assays used.

  9. Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan

    Science.gov (United States)

    Hoshi, Shu-ling; Kondo, Masahide; Okubo, Ichiro

    2015-01-01

    Background Currently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV–23) and 13-valent pneumococcal conjugate vaccine (PCV–13) are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV–23 was approved in 1988, while the extended use of PCV–13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV–23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV–23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot. Methods We performed economic evaluations to (1) evaluate the efficiency of alternative strategies of PPSV–23 single-dose immunisation programme, and (2) investigate the efficiency of PCV–13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1) current PPSV–23 strategy, (2) 65 to 80 (as “65–80 PPSV–23 strategy”), and (3) 65 and older (as “≥65 PPSV–23 strategy”). We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥8,116 (US$74; US$1 = ¥110) for PPSV–23 and ¥10,776 (US$98) for PCV–13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%. Results Compared to current PPSV–23 strategy, 65–80 PPSV–23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs) of ≥65 PPSV–23 strategy was ¥5,025,000 (US$45

  10. Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan.

    Directory of Open Access Journals (Sweden)

    Shu-ling Hoshi

    Full Text Available Currently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV-23 and 13-valent pneumococcal conjugate vaccine (PCV-13 are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV-23 was approved in 1988, while the extended use of PCV-13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV-23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV-23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥ 100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot.We performed economic evaluations to (1 evaluate the efficiency of alternative strategies of PPSV-23 single-dose immunisation programme, and (2 investigate the efficiency of PCV-13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1 current PPSV-23 strategy, (2 65 to 80 (as "65-80 PPSV-23 strategy", and (3 65 and older (as "≥ 65 PPSV-23 strategy". We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥ 8,116 (US$74; US$1 = ¥ 110 for PPSV-23 and ¥ 10,776 (US$98 for PCV-13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%.Compared to current PPSV-23 strategy, 65-80 PPSV-23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs of ≥ 65 PPSV-23 strategy was ¥ 5,025,000 (US$45,682 per QALY gained. PCV-13 inclusion into the list for

  11. The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial

    Science.gov (United States)

    Mentzer, Alexander J.; Lule, Swaib A.; Kizito, Dennison; Smits, Gaby; van der Klis, Fiona R. M.; Elliott, Alison M.

    2017-01-01

    Background Chronic parasitic infections are associated with active immunomodulation which