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Sample records for bacille calmette-guerin bcg

  1. Bacille-Calmette-Guerin non-responders: how to manage

    OpenAIRE

    von Rundstedt, Friedrich-Carl; Lerner, Seth P.

    2015-01-01

    Intravesical immunotherapy with bacille-Calmette-Guerin (BCG) is indicated in the treatment of high-risk and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Our goal is to describe the various disease states following induction and maintenance BCG and to describe contemporary treatment options and the current and projected clinical trial landscape for patients who recur following BCG therapy.

  2. Fecal volatile organic compound profiles from white-tailed deer (Odocoileus virginianus) as indicators of Mycobacterium bovis exposure or Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccination

    Science.gov (United States)

    White-tailed deer (Odocoileus virginianus) serve as a reservoir for bovine tuberculosis, caused by Mycobacterium bovis, and can be a source of infection in cattle. Vaccination with M. bovis bacille Calmette-Guerin (BCG) is being considered for management of bovine tuberculosis in deer. Presently, no...

  3. Various ultrasonographic manifestations of Bacille Calmette-Guerin (BCG) lymphadenitis in infants after BCG vaccination

    International Nuclear Information System (INIS)

    To evaluate the various ultrasonographic manifestations of BCG lymphadenitis complicated by BCG vaccination in infants. Among a total of 59 patients of BCG lymphadenitis, we retrospectively evaluated the ultrasonographic findings of five patients (seven involved areas), who were operated and confirmed by histopathology. Three cases were male and two were female and the age range is from 3 months to 9 months (mean: 5.5 months). Among five cases two had only a single lesion and three had multiple lesions, and two of those had multiple lesions at 2 separate locations. All five cases had ipsilateral supraclavicular lesions with same BCG vaccination site and two also had ipsilaeteral axillary lesions. Ultrasonography showed enlarged lymph nodes and heterogeneous hypoechoic changes suggesting internal necrosis or suppurative changes in three cases, but 1 had cystic necrotic change with fluid-fluid level and another had conglomerated mass with intermingled hyper and hypoechoic areas, which were initially suspected to be a tumorous conditions but revealed conglomerated lymph nodes on follow-up ultrasonography and MRI. BCG lymphadenitis is usually located adjacent to a BCG vaccination site, but ultrasonography can show single or multiple lymph node enlargement and various manifestations from homogeneous lymphadenitis to cystic abscess changes and even a mass-like appearance, demonstrating that the evaluation of ultrasonography should be done very carefully.

  4. Clinical features and outcome of eleven patients with disseminated Bacille Calmette-Guerin (BCG) infection

    International Nuclear Information System (INIS)

    Disseminated BCG infection is a very rare complication of BCG vaccination. This study presents 11 patients with such complication. The underlying disease in eight of the 11 patients was primary immunodeficiency. Seven of these had severe combined immune deficiency (SCID) and one had isolated T-cell defect. Of the three remaining patients, one was healthy, one was diagnosed with mucocutaneous candidiasis and the third was diagnosed with leukocytoclastic vasculitis. Cutaneous nodular lesion, persistent fever, hepatosplenomegaly and pulmonary symptoms were common presenting features. All but one patient received antituberculous treatment. Four of 11 patients died because of extensive BCG disease. Three of these had SCID and one had T-cell deficiency. Patients with SCID who survived had bone marrow transplantation in addition to antituberculous chemotherapy. We conclude that a family history of immunodeficiency should be sought and if suggestive, BCG vaccine should be deferred until the immune status of the baby is clarified. In addition, early diagnosis is important for successful outcome. Bone marrow transplant on an emergency basis is the treatment of choice in patients with SCID and disseminated BCG infection, as immune reconstitution is essential to control infection in these patients. (author)

  5. Suppurative supraclavicular bacille calmette-guerine lymphadenitis - A case report, awareness and management options

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    U S Udgaonkar

    2015-01-01

    Full Text Available Diagnosis of Bacille calmette-guerine (BCG adenitis is clinical. Conventional laboratory tests do not differentiate BCG adenitis from tuberculous adenitis. We report a case of a 3-month-old healthy baby presenting with suppurative BCG adenitis. FNAC revealed AFB on ZN-Staining, later confirmed to be Mycobacterium bovis by multiplex PCR. The treatment of suppurative BCG adenitis is needle aspiration. Anti-tubercular treatment is unwarranted.

  6. Fecal Volatile Organic Ccompound Profiles from White-Tailed Deer (Odocoileus virginianus) as Indicators of Mycobacterium bovis Exposure or Mycobacterium bovis Bacille Calmette-Guerin (BCG) Vaccination.

    Science.gov (United States)

    Stahl, Randal S; Ellis, Christine K; Nol, Pauline; Waters, W Ray; Palmer, Mitchell; VerCauteren, Kurt C

    2015-01-01

    White-tailed deer (Odocoileus virginianus) serve as a reservoir for bovine tuberculosis, caused by Mycobacterium bovis, and can be a source of infection in cattle. Vaccination with M. bovis Bacille Calmette Guerin (BCG) is being considered for management of bovine tuberculosis in deer. Presently, no method exists to non-invasively monitor the presence of bovine tuberculosis in deer. In this study, volatile organic compound profiles of BCG-vaccinated and non-vaccinated deer, before and after experimental challenge with M. bovis strain 95-1315, were generated using solid phase microextraction fiber head-space sampling over suspended fecal pellets with analysis by gas chromatography/mass spectrometry. Chromatograms were processed using XCMS Online to characterize ion variation among treatment groups. The principal component scores resulting from significant (α = 0.05) ion responses were used to build linear discriminant analysis models. The sensitivity and specificity of these models were used to evaluate the feasibility of using this analytical approach to distinguish within group comparisons between pre- and post-M. bovis challenge: non-vaccinated male or female deer, BCG-vaccinated male deer, and the mixed gender non-vaccinated deer data. Seventeen compounds were identified in this analysis. The peak areas for these compounds were used to build a linear discriminant classification model based on principal component analysis scores to evaluate the feasibility of discriminating between fecal samples from M. bovis challenged deer, irrespective of vaccination status. The model best representing the data had a sensitivity of 78.6% and a specificity of 91.4%. The fecal head-space sampling approach presented in this pilot study provides a non-invasive method to discriminate between M. bovis challenged deer and BCG-vaccinated deer. Additionally, the technique may prove invaluable for BCG efficacy studies with free-ranging deer as well as for use as a non

  7. Peripheral blood and marrow findings in disseminated bacille Calmette-Guerin infection.

    Science.gov (United States)

    Kumar, Perikala Vijayananda; Monabati, Ahmad; Kadivar, Rahim; Soleimanpour, Hossein

    2005-02-01

    The authors describe an unusual case of a disseminated bacille Calmette-Guerin (BCG) infection in a 3-month-old girl who presented with a huge hepatosplenomegaly, fever, and pancytopenia. Clinically, an infantile kala-azar or lymphoma/leukemia was suspected. However, after thorough clinical and paraclinical investigations, the case was diagnosed as a disseminated BCG infection. The child died 2 weeks after starting antituberculosis treatment. Autopsy revealed diffuse histiocytic infiltration in the liver, spleen, and mesenteric lymph nodes, which were loaded with acid-fast bacilli. Three interesting findings were noticed in this case: circulating monocytes in the peripheral blood were loaded with ghost acid-fast bacilli; bone marrow smears revealed numerous Gaucher cell-like macrophages loaded with negative images of Mycobacterium tuberculi; and there was extensive marrow necrosis. These findings have not been previously reported in the literature.

  8. BCG (Bacille Calmette-Guerin) Vaccine

    Science.gov (United States)

    ... American Community Summit Background Slideset Children Correctional Facilities Homelessness International Travelers Pregnancy Health Disparities Laboratory Information Model Performance Evaluation Program (MPEP) Drug Susceptibility Testing The Uses of Nucleic Acid Amplification ...

  9. 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.

  10. Upregulation of TNF-αand IL-6 mRNA in mouse liver induced by bacille Calmette-Guerin plus lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    Dao-fang LIU; Wei WEI; Li-hua SONG

    2006-01-01

    Aim:To investigate the mechanism of immunological liver injury induced by bacille Calmette-Guerin (BCG) plus lipopolysaccharide (LPS).Methods:Mice were injected via the tail vein with 125 mg/kg BCG,and 12 d later,the mice were injected intravenously with different doses of LPS (125,250.or 375 μg/kg).Serum alanine aminotransferase (ALT) activity and liver pathological changes were examined.The expression of tumor necrosis factor (TNF)-α,interleukin (IL)-6,lipopolysaccharide binding protein (LBP) and CD14 mRNA,and NF-κB and IκB-α protein in mouse liver at difierent time points after BCG and LPS injection were measured using RT-PCR,immunohistochemistry and Western blotting analysis,respectively.Results:The activity of serum ALT in mice treated witll BCG and LPS was significantly increased.Different degrees of liver injury,such as inflammatory cell infiltration,spotty necrosis,piecemeal necrosis,even bridging necrosis,could be seen in liver sections from mice after BCG and LPS administration.Furthermore,the levels of TNF-α and IL-6 mRNA in mouse liver were significantly elevated after administration of BCG plus LPS (P<0.05).The levels of LBP and CD14 mRNA in mouse liver were markedly upregulated after treatment with BCG and LPS.and treatment with BCG alone led to an increase in CD14 mRNA in mouse liver.Finally.immunoreactivity for NF-κB p65 was predominantly detected in hepatocyte nuclei from mice treated with BCG plus LPS,compared with the normal group.Protein levels of IκB-α were strikingly decreased by LPS or BCG plus LPS treatment.compared with the normal group or BCG group.Conclusion:TNF-α and IL-6 mRNA were partially involved in early immunological liver injury induced by chal lenge with small doses of LPS after BCG priming.Upregulation of TNF-α and IL6 mRNA might be related to increases in LBP and CD14 mRNA expression and activation of NF-kB.Furthermore,BCG priming in immunological liver injury may occur via upregulation of CD14 mRNA expression in

  11. Combination therapy using intratumoral bacillus Calmette-Guerin (BCG) and vincristine in dogs with transmissible venereal tumours : therapeutic efficacy and histological changes : article

    OpenAIRE

    S. Mukaratirwa; S. Chitanga; T. Chimatira; C. Makuleke; S.T. Sayi; E. Bhebhe

    2009-01-01

    Therapeutic efficacy and histological changes after bacillus Calmette-Guerin (BCG), vincristine and BCG/vincristine combination therapy of canine transmissible venereal tumours (CTVT) were studied. Twenty dogs with naturally occurring CTVT in the progression stage were divided into 4 groups and treated with intratumoral BCG, vincristine, BCG/vincristine combination therapy or intratumoral buffered saline (control group). Tumour sizes were determined weekly and tumour response to therapy was a...

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

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    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

  13. Mycobacterium bovis-Bacillus Calmette-Guerin and asthma

    Institute of Scientific and Technical Information of China (English)

    SHEN Hua-hao; ZHANG Gen-sheng; WANG Ping-li

    2005-01-01

    @@ In recent decades, the prevalence of asthma over the world has risen steadily especially in high-income countries.1 The underlying mechanisms for this phenomenon remain largely unknow, but environmental factors are thought to play an important role. Some epidemiology studies2-8 suggested that the increase in asthma inversely correlated with a steady decline exposition to some human diseases, such as tuberculosis and influenza. One of the general features of these infectious agents is that they induce characteristic Th1 type immune response which suppresses the Th2 response predominate in individuals suffering from asthma. Bacille Calmette-Guerin(BCG) is a strong inducer of Th1 type immune response. This review will focus on recent findings related to the interaction between BCG and asthma, and the main mechanisms of BCG in modulating asthma development.

  14. Effect of high-dose vitamin A supplementation on the immune response to Bacille Calmette-Guerin vaccine

    DEFF Research Database (Denmark)

    Diness, Birgitte R; Fisker, Ane B; Roth, Adam;

    2007-01-01

    scar was not affected by VAS. The ex vivo interferon-gamma response to PPD was increased by VAS (means ratio: 1.40; 95% CI: 1.03, 1.91). CONCLUSIONS: VAS with BCG vaccination does not appear to interfere with the long-term immune response to BCG. However, VAS temporarily altered the DTH reaction to PPD...... objective was to examine whether VAS influences the immune response to simultaneously administered BCG vaccine. DESIGN: Within a randomized trial of 50,000 IU vitamin A or placebo given with BCG vaccine at birth in Guinea-Bissau, 2710 infants were examined for BCG scar formation and delayed...

  15. Oral vaccination of white-tailed deer (Odocoileus virginianus with Mycobacterium bovis Bacillus Calmette-Guerin (BCG.

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    Mitchell V Palmer

    Full Text Available Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis from livestock, particularly cattle. In Michigan, USA tuberculous white-tailed deer transmit M. bovis to other deer and cattle. One approach in dealing with this wildlife reservoir is to vaccinate deer, thus interfering with the intraspecies and interspecies transmission cycles. Thirty-three white-tailed deer were assigned to one of two groups; oral vaccination with 1 × 10(8 colony-forming units of M. bovis BCG Danish (n = 17; and non-vaccinated (n = 16. One hundred eleven days after vaccination deer were infected intratonsilarly with 300 colony-forming units of virulent M. bovis. At examination, 150 days after challenge, BCG vaccinated deer had fewer gross and microscopic lesions, fewer tissues from which M. bovis could be isolated, and fewer late stage granulomas with extensive liquefactive necrosis. Fewer lesions, especially those of a highly necrotic nature should decrease the potential for dissemination of M. bovis within the host and transmission to other susceptible hosts.

  16. 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....

  17. Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial

    NARCIS (Netherlands)

    Biering-Sorensen, S.; Jensen, K.J.; Aamand, S.H.; Blok, B.; Andersen, A.; Monteiro, I.; Netea, M.G.; Aaby, P.; Benn, C.S.; Haslov, K.R.

    2015-01-01

    INTRODUCTION: Bacille Calmette-Guerin (BCG) vaccine has beneficial non-specific effects on overall survival. After BCG vaccination, positive PPD response and scar formation are associated with increased survival. During a trial randomising low-birth-weight neonates to BCG at birth or the usual delay

  18. Treatment Options Available for Bacillus Calmette-Guerin Failure in Non-muscle-invasive Bladder Cancer

    NARCIS (Netherlands)

    Yates, D.R.; Brausi, M.A.; Catto, J.W.; Dalbagni, G.; Roupret, M.; Shariat, S.F.; Sylvester, R.J.; Witjes, J.A.; Zlotta, A.R.; Palou-Redorta, J.

    2012-01-01

    CONTEXT: Intravesical bacillus Calmette-Guerin (BCG) is a standard conservative treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Many patients will experience recurrence or progression following BCG and are termed BCG failures. OBJECTIVE: To summarise the current tre

  19. Perbedaan Kadar Interferon Gamma dan Interleukin-10 pada Orang Dewasa Terinfeksi Ascaris Lumbricoides dengan Tidak Terinfeksi yang Diinduksi Vaksin Bacille Calmette-Guerin

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    weni Mulyani; Nuzulia Irawati; Netti Suharti

    2015-01-01

    Abstrak Kecacingan merupakan penyakit yang masih banyak di negara berkembang. Infeksi cacing dapat menimbulkan penurunan respon terhadap antigen yang terjadi akibat modified Th2 response. Vaksin BCG merupakan antigen yang dikenal sebagai penginduksi respon sel Th1. Tujuan penelitian ini adalah untuk mengetahui perbedaan kadar IFN-γdan IL-10 pada orang dewasa terinfeksi Ascaris lumbricoides dengan tidak terinfeksi yang diinduksi vaksi BCG.Penelitian dilakukan di Kelurahan Muara Fajar Kecamatan...

  20. Revaccination of cattle with bacille Calmette-Guerin two years after first vaccination when immunity has waned, boosted protection against challenge with Mycobacterium bovis.

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    Natalie A Parlane

    Full Text Available In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 2½ years after vaccination and to determine the effect of revaccination after 2 years. Seventy-nine calves were divided into five groups (n = 15-17 calves/group with four of the groups vaccinated subcutaneously with 105 CFU of BCG Danish at 2-4 weeks of age and the fifth group serving as non-vaccinated controls. Three of the four BCG-vaccinated groups were revaccinated 2 years after the initial vaccination. One BCG-vaccinated group was revaccinated with BCG. A second group was vaccinated subcutaneously with a TB protein vaccine consisting of biopolyester particles (Biobeads displaying two mycobacterial proteins, ESAT-6 and Antigen 85A, mixed with an adjuvant. A third group was vaccinated with TB proteins from M. bovis culture filtrate, mixed with an adjuvant. Twenty-three weeks after the BCG revaccination, all animals were challenged endotracheally with virulent M. bovis and a further 13 weeks later, animals were killed and necropsied to determine protection against TB. The BCG-vaccinated animals produced positive tuberculin caudal fold intradermal (15 of 62 animals and IFN-γ TB test responses (six of 62 animals at 6 months after vaccination, but not at subsequent time-points compared to the non-vaccinated animals. Calves receiving a single vaccination with BCG vaccine 2½ years prior to challenge were not protected against TB, while those revaccinated with BCG 2 years after the initial vaccination displayed significant reductions in lung and pulmonary lymph node lesion scores compared to the non-vaccinated animals. In contrast, no reduction in lesion scores was observed in the animals revaccinated with the TB protein vaccines with

  1. THE CONSTRUCTION AND EXPRESSION OF RECOMBINANT SHUTTLE PLASMID WITH OMPL1 GENE FROM LEPTOSPIRA INTERROGANS SEROVAR LAI STRAIN 017 IN BACILLE CALMETTE GUERIN

    Institute of Scientific and Technical Information of China (English)

    鲍朗; 邱洪宇; 晏菊芳; 谢勇恩; 陈玮

    2002-01-01

    Objective.To construct recombinant BCG against leptospirosis.Methods.We amplified the entire open reading frame of the OmpL1 gene from the genome of the leptospire serovar Lai strain 017.Two recombinant plasmids pBQ1 and pBQ2 were constructed by oriented ligation based on the E.coli BCG shuttle plasmids pMV261 and pMV361 respectively.The recombinant plasmids were transformed into BCG by electroporation.The rBCGs bearing pBQ1 and pBQ2 were induced by high temperature of 45℃ .Results.The expressed product,a 35kD protein was detected by SDS PAGE.The result indicates that pBQ1 and pBQ2 can express OmpL1 in rBCG.Conclusion.The technical methods in this study may help detect the immunogenicity and immunoprotection of OmpL1 and develop more safe,highly effective rBCG bearing leptospiral antigen with long lasting protection.

  2. Study on pre-immunization with Bacillus Calmette-Guerin (BCG) on Candida albicans infection in mice%卡介苗免疫预防小鼠白色念珠菌感染的实验研究

    Institute of Scientific and Technical Information of China (English)

    李丽波; 王玉祥

    2009-01-01

    目的 探讨卡介苗(BCG)预先免疫对小鼠白色念珠菌感染的影响.方法 采用BCG或灭菌生理盐水皮内注射预先免疫2周,然后由尾静脉注射白色念珠菌进行攻击,观察小鼠死亡率及计算存活小鼠肾组织带菌量.结果 BCG免疫组存活时间长于生理盐水免疫组(P<0.01);存活小鼠肾组织菌落计数:BCG免疫组远少于省里盐水免疫组(P<0.01).结论 BCG对小鼠白色念珠菌感染具有很好的保护作用.%Objective To investigate the effect of preimmunization with Bacillus Calmette-Guerin (BCG) on Candida albicans infection in mice. Methods BCG or 0.9% sterile saline was injected intracutaneously to ICR mice for preimmunization for two weeks before inoculation of Candida albicans by vena caudalis injection, then mortality rate of mice was observed and Candida albicans in mice kidney was examined. Results Survival time in BCG preimmunization group was longer than that in 0.9% sterile saline group (P<0.01); colony count of Candida albicans in mice kidney in BCG preimmunization group was less than that in saline group (P < 0.01). Conclusions BCG pre-immunization has protective effect from Candida albicans infection in mice.

  3. Perbedaan Kadar Interferon Gamma dan Interleukin-10 pada Orang Dewasa Terinfeksi Ascaris Lumbricoides dengan Tidak Terinfeksi yang Diinduksi Vaksin Bacille Calmette-Guerin

    OpenAIRE

    Weni Mulyani; Nuzulia Irawati; Netti Suharti

    2016-01-01

    AbstrakKecacingan merupakan penyakit yang masih banyak di negara berkembang. Penyakit ini dapat menimbulkan gangguan gizi, pertumbuhan dan penurunan produktifitas kerja. Infeksi cacing dapat menimbulkan penurunan respon terhadap antigen sebagai akibat modified Th2 response. Vaksin BCG merupakan antigen yang dikenal sebagai penginduksi respon sel Th1. Tujuan penelitian ini adalah menentukan perbedaan kadar IFN-γ dan IL-10 antara orang dewasa terinfeksi Ascaris lumbricoides dan tidak terinfeksi...

  4. Trained immunity: consequences for the heterologous effects of BCG vaccination

    NARCIS (Netherlands)

    Kleinnijenhuis, J.; Crevel, R. van; Netea, M.G.

    2015-01-01

    A growing body of evidence from epidemiologic and immunologic studies have shown that in addition to target disease-specific effects, vaccines have heterologous effects towards unrelated pathogens. Like some other vaccines, bacille Calmette-Guerin (BCG) has shown in observational studies and randomi

  5. Accuracy of the QuantiFERON-TB Gold in Tube for diagnosing tuberculosis in a young pediatric population previously vaccinated with Bacille Calmette-Guerin

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    Marcelo Genofre Vallada

    2014-03-01

    Full Text Available Objective: To evaluate the accuracy of an interferongamma release assay (QuantiFERON-TB Gold in Tube for diagnosing Mycobacterium tuberculosis infection in a young pediatric population. Methods: 195 children previously vaccinated with BCG were evaluated, being 184 healthy individuals with no clinical or epidemiological evidence of mycobacterial infection, and 11 with Mycobacterium tuberculosis infection, according to clinical, radiological, and laboratory parameters. A blood sample was obtained from each child and processed according to the manufacturer's instructions. The assay performance was evaluated by a Receiver Operating Characteristic (ROC curve. Results: In the group of 184 non-infected children, 130 (70.6% were under the age of four years (mean age of 35 months. In this group, 177 children (96.2% had negative test results, six (3.2% had indeterminate results, and one (0.5% had a positive result. In the group of 11 infected children, the mean age was 58.5 months, and two of them (18% had negative results. The ROC curve had an area under the curve of 0.88 (95%CI 0.82-0.92; p<0.001, disclosing a predictive positive value of 81.8% for the test (95%CI 46.3-97.4. The assay sensitivity was 81.8% (95%CI 48.2-97.2 and the specificity was 98.8% (95%CI 96-99.8. Conclusions: In the present study, the QuantiFERON-TB Gold in Tube performance for diagnosing M. tuberculosis infection was appropriate in a young pediatric population.

  6. 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

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    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.

  7. Revisiting the structure of the anti-neoplastic glucans of Mycobacterium bovis Bacille Calmette-Guerin. Structural analysis of the extracellular and boiling water extract-derived glucans of the vaccine substrains.

    Science.gov (United States)

    Dinadayala, Premkumar; Lemassu, Anne; Granovski, Pierre; Cérantola, Stéphane; Winter, Nathalie; Daffé, Mamadou

    2004-03-26

    The attenuated strain of Mycobacterium bovis Bacille Calmette-Guérin (BCG), used worldwide to prevent tuberculosis and leprosy, is also clinically used as an immunotherapeutic agent against superficial bladder cancer. An anti-tumor polysaccharide has been isolated from the boiling water extract of the Tice substrain of BCG and tentatively characterized as consisting primarily of repeating units of 6-linked-glucosyl residues. Mycobacterium tuberculosis and other mycobacterial species produce a glycogen-like alpha-glucan composed of repeating units of 4-linked glucosyl residues substituted at some 6 positions by short oligoglucosyl units that also exhibits an anti-tumor activity. Therefore, the impression prevails that mycobacteria synthesize different types of anti-neoplastic glucans or, alternatively, the BCG substrains are singular in producing a unique type of glucan that may confer to them their immunotherapeutic property. The present study addresses this question through the comparative analysis of alpha-glucans purified from the extracellular materials and boiling water extracts of three vaccine substrains. The polysaccharides were purified, and their structural features were established by mono- and two-dimensional NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of the enzymatic and chemical degradation products of the purified compounds. The glucans isolated by the two methods from the three substrains of BCG were shown to exhibit identical structural features shared with the glycogen-like alpha-glucan of M. tuberculosis and other mycobacteria. Incidentally, we observed an occasional release of dextrans from Sephadex columns that may explain the reported occurrence of 6-substituted alpha-glucans in mycobacteria.

  8. Routine Transurethral Biopsy of the Bladder is not Necessary to Evaluate the Response to Bacillus Calmette-guerin Therapy

    OpenAIRE

    Murakami, Takanori; Ebara, Shin; Saika, Takashi; IRIE, Shin (Keio University, Japan); Takeda, Katsuji; Maki, Yoshio; Miyaji, Sadayuki; Manabe, Daisuke; Kaku,Haruki; Nasu, Yasutomo; Tsushima, Tomoyasu; Kumon, Hiromi

    2007-01-01

    We evaluated the need for transurethral biopsy at first follow-up after intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. The records of 84 patients with superficial bladder cancer who received a 6- or 8-week course of BCG were reviewed. Pathological results before BCG, cystoscopic findings, urinary cytology, and biopsy results for evaluation of BCG therapy were reviewed. All 19 patients with positive urinary cytology had evidence of positive bladder biopsy r...

  9. Granulomatous epididymo-orchitis, a rare complication of intravesical bacillus Calmette-Guerin therapy for urothelial cancer

    DEFF Research Database (Denmark)

    Harving, S.S.; Asmussen, L.; Roosen, Jens Ulrik;

    2009-01-01

    Only a few cases of tuberculous epididymo-orchitis after bacillus Calmette-Guerin (BCG) therapy have been published. This report presents a case of granulomatous epididymo-orchitis after intravesical BCG therapy in a patient presenting with pain and unilateral swelling of the scrotal content. Thi...... complication should always be considered when a patient presents with these symptoms after BCG therapy. Isoniazid may be used as a first choice of treatment Udgivelsesdato: 2009......Only a few cases of tuberculous epididymo-orchitis after bacillus Calmette-Guerin (BCG) therapy have been published. This report presents a case of granulomatous epididymo-orchitis after intravesical BCG therapy in a patient presenting with pain and unilateral swelling of the scrotal content. This...

  10. Disseminated bacillus calmette guerin disease in a twin infant with severe combined immunodeficiency disease

    Directory of Open Access Journals (Sweden)

    Hema Mittal

    2014-01-01

    Full Text Available Fatal-disseminated Bacillus Calmette Guerin (BCG disease is well known in infants with severe combined immunodeficiency after BCG vaccination. We report a 7 month male infant delivered as a product of in vitro fertilization and twin gestation that presented with fever, cough and multiple nodular skin lesions. A biopsy of skin lesions revealed the presence of acid fast bacilli. Mycobacterium bovis infection was confirmed by polymerase chain reaction (PCR and molecular studies. Immunological profile confirmed the diagnosis of severe combined immunodeficiency. Only few reports of similar case exist in the literature.

  11. Diffuse Hyperpigmented Subcutaneous Nodules as a Primary Manifestation of Disseminated Bacillus Calmette-Guerin Disease in Young Infants

    Directory of Open Access Journals (Sweden)

    Rafiei Tabatabaei

    2015-08-01

    Full Text Available Introduction There are increasing reports of serious adverse events of bacillus Calmette-Guerin (BCG vaccination in infants with unrecognized primary immunodeficiency disorders (PIDs in our country. Among these adverse events skin manifestations occur less frequently and are less noticed. Case Presentation We report on an 11-months-old boy with prolonged fever and diffuse hyperpigmented subcutaneous nodules. Due to lymphopenia, oral thrush and severe adverse reaction to BCG vaccination, the possibility of primary immunodeficiency was considered for him and immunological investigations were done. Conclusions Subcutaneous nodules in the absence of a local reaction at the site of BCG vaccination may be the sole manifestation of disseminated BCG disease.

  12. FNAC of Bacillus- Calmette- Guerin lymphadenitis masquerading as Langerhans cell histiocytosis.

    Directory of Open Access Journals (Sweden)

    Gupta Nalini

    2004-12-01

    Full Text Available Abstract Bacillus Calmette Guerin (BCG lymphadenitis is a well known entity. Disseminated BCG infection usually presents as generalized lymphadenopathy, skin rash and hepatosplenomegaly and at times, can pose a diagnostic challenge to clinicians. There are only a few published studies on the cytological findings of BCG lymphadenitis. In this letter we report the fine needle aspiration cytology (FNAC of BCG lymphadenitis clinically masquerading as Langerhans cell histiocytosis (LCH. FNA smears showed sheets of foamy macrophages and many polymorphs in a dirty necrotic background with many macrophages as well as polymorphs showing negatively stained rod like structures within their cytoplasm. Zeihl Neelson stain revealed that these cells were heavily loaded with acid fast bacilli (AFB. In the index case, AFB were also seen within the cytoplasm of polymorphs, which has not been documented earlier in the literature.

  13. Multiphase contrast-enhanced magnetic resonance imaging features of Bacillus Calmette-Guerin-induced granulomatous prostatitis in five patients

    Energy Technology Data Exchange (ETDEWEB)

    Kawada, Hiroshi; Kanematsu, Masayuki; Goshima, Satoshi; Kondo, Hiroshi; Watanabe, Haruo; Noda, Yoshifumi; Tanahashi, Yukichi; Kawai, Nobuyuki; Hoshi, Hiroaki [Gifu University Hospital, Gifu (Japan)

    2015-04-15

    To evaluate the multiphase contrast-enhanced magnetic resonance (MR) imaging features of Bacillus Calmette-Guerin (BCG)-induced granulomatous prostatitis (GP). Magnetic resonance images obtained from five patients with histopathologically proven BCG-induced GP were retrospectively analyzed for tumor location, size, signal intensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI), apparent diffusion coefficient (ADC) value, and appearance on gadolinium-enhanced multiphase images. MR imaging findings were compared with histopathological findings. Bacillus Calmette-Guerin-induced GP (size range, 9-40 mm; mean, 21.2 mm) were identified in the peripheral zone in all patients. The T2WI showed lower signal intensity compared with the normal peripheral zone. The DWIs demonstrated high signal intensity and low ADC values (range, 0.44-0.68 x 10(-3) mm2/sec; mean, 0.56 x 10(-3) mm2/sec), which corresponded to GP. Gadolinium-enhanced multiphase MR imaging performed in five patients showed early and prolonged ring enhancement in all cases of GP. Granulomatous tissues with central caseation necrosis were identified histologically, which corresponded to ring enhancement and a central low intensity area on gadolinium-enhanced MR imaging. The findings on T2WI, DWI, and gadolinium-enhanced images became gradually obscured with time. Bacillus Calmette-Guerin-induced GP demonstrates early and prolonged ring enhancement on gadolinium-enhanced MR imaging which might be a key finding to differentiate it from prostate cancer.

  14. Neonatal bacillus Calmette-Guerin vaccination inhibits de novo allergic inflammatory response in mice via alteration of CD4+CD25+T-regulatory cells

    Institute of Scientific and Technical Information of China (English)

    Qian LI; Hua-hao SHEN

    2009-01-01

    Aim: The hygiene hypothesis suggests a lack of bacterial infections would favor the development of allergic diseases. My-cobacterium bovis bacille Calmette-Guerin (BCG) infection can inhibit allergen-induced asthma reactions, but the underly-hag mechanism of this infection on the immunological responses is unclear. T-regulatory (Treg) cells are thought to play a role as a crucial immunoregulatory cells that are capable of regulating adaptive immune responses. We conducted this study to investigate whether the protective effect of the BCG vaccination on allergic pulmonary inflammation is associated with the alteration of CD4+CD25+ Treg cells in a murine asthma model and the mechanisms of Treg cells. Methods: Newborn C57BL/6 mice were vaccinated 3 times with BCG on d 0, 7, and 14 and subsequently sensitized and challenged with ovalbumin. Eosinophil infiltration was investigated. The frequencies of spleen CD4+CD25+ Treg cells and the expression of specific transcriptional factor Foxp3 were assayed. The cytotoxic lymphocyte associated antigen (CTLA)-4 expression and cytokine interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) levels were measured. Results: We showed that treatment of mice with BCG inhibited de novo allergic inflammatory response in a mouse model of asthma. BCG treatments are associated with the increase of CD4+CD25+ Treg cells and Foxp3 expression, accompanied by an increased CTLA-4 expression and cytokine IL-10 and TGF-β levels (P<0.05). Conclusion: Neonatal BCG vaccinations ameliorate de novo local eosinophilic inflammation induced by allergen and in-crease the numbers of CD4+CD25+ Treg cells and Foxp3 expression. The cell-cell contact inhibition and regulatory cytokine production may be involved in the regulatory mechanism.

  15. Comparison of intravesical bacillus Calmette-Guerin and mitomycin C administration for non-muscle invasive bladder cancer: A meta-analysis and systematic review

    OpenAIRE

    JIANG, SHANG-JUN; YE, LI-YIN; Meng, Fan-Hua

    2016-01-01

    The aim of the present meta-analysis was to compare the benefits of Bacillus Calmetter-Guerin (BCG) and mitomycin C in the treatment of patients with superficial bladder cancer. The present meta-analysis analyzed the benefits of BCG and mitomycin C in the treatment of patients with superficial bladder cancer by comparing progression-free survival (PFS) rates in patients treated with either of the drugs following transurethral resection. The Medline, Cochrane and EMBASE databases were searched...

  16. Routine Transurethral Biopsy of the Bladder is not Necessary to Evaluate the Response to Bacillus Calmette-guerin Therapy

    Directory of Open Access Journals (Sweden)

    Manabe,Daisuke

    2007-12-01

    Full Text Available We evaluated the need for transurethral biopsy at first follow-up after intravesical bacillus Calmette-Guerin (BCG therapy for superficial bladder cancer. The records of 84 patients with superficial bladder cancer who received a 6- or 8-week course of BCG were reviewed. Pathological results before BCG, cystoscopic findings, urinary cytology, and biopsy results for evaluation of BCG therapy were reviewed. All 19 patients with positive urinary cytology had evidence of positive bladder biopsy results. Fifty-three of 54 patients (98.1% with no visible recurrent tumor and negative urinary cytology demonstrated negative pathological results on bladder biopsy. When not found in conjunction with positive urinary cytology, erythematous mucosa on cystoscopy was not an indicator of tumor recurrence or residual cancer. In conclusion, routine transurethral biopsy of the bladder for evaluating the response to BCG intravesical therapy is not necessary in patients who have no visible tumor on cystoscopy and negative urinary cytology./

  17. Bacillus Calmette-Guerin lymphadenitis: A 6-year experience in two Saudi hospitals

    Directory of Open Access Journals (Sweden)

    E Bukhari

    2012-01-01

    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 : We evaluated the frequency, the clinical presentation and treatment modalities of lymphadenitis after BCG vaccine in Saudi children. Results : A total of 145 patients with BCG lymphadenitis presented between January 2005 and December 2010. In the majority (103 of the cases, the lymphadenitis involved ipsilateral left axillary nodes. Other sites of involvement included the left supraclavicular lymph nodes in 26 (18% patients, and both the left axillary and supraclavicular lymph nodes were involved in 7 cases (4.8%. A total of 75 patients (65% were given antituberculous medication. Eight (27% patients had positive acid-fast bacilli and positive cultures for Mycobacterium bovis. Conclusion : In light of the findings of this study, it would be advisable to administer the BCG vaccine in Saudi Arabia at a time later than at birth, as the younger children are commonly affected.

  18. Mesane içine Bacillus Calmette-Guerin uygulanması sonrası gelişen reaktif artrit: Bir olgu sunumu

    OpenAIRE

    Tunç, Ş.Ercan; Arslan, Çağatay; Şahin, Mehmet; Adiloğlu, Ali Kudret

    2009-01-01

    SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 2004 Eylül; 11(3) Mesane içine Bacillus Calmette-Guerin uygulanması sonrası gelişen reaktif artrit: Bir olgu sunumu Ş.Ercan Tunç, Çağatay Arslan, Mehmet Şahin, Ali Kudret Adiloğlu Özet Bacillus Calmette-Guerin (BCG) uygulaması süperfisiyal mesane karsinomlarında kullanılan etkin bir tedavi metodudur. Bu tedavi sırasında nadiren reaktif olarak artrit ve artraljiler gelişebilmektedir. Burada, mesaneye dördü...

  19. Visible and subvisible particles in the BCG immunotherapeutic product Immucyst®.

    Science.gov (United States)

    Kirkitadze, Marina; Remi, Elena; Bhandal, Kamajit; Carpick, Bruce

    2016-01-01

    Bacille Calmette-Guerin, BCG, is a live attenuated bovine tubercle bacillus used for the treatment of non-muscle invasive bladder cancer. In this study, an Electrical Sensing Zone (ESZ) method was developed to measure the particle count and the size of BCG immunotherapeutic (BCG IT), or ImmuCyst® product using a Coulter Counter Multisizer 4® instrument. The focus of this study was to establish a baseline for reconstituted lyophilized BCG IT product using visible and sub-visible particle concentration and size distribution as reportable values. ESZ method was used to assess manufacturing process consistency using 20 production scale lots of BCG IT product. The results demonstrated that ESZ can be used to accumulate product and process knowledge of BCG IT. PMID:27158432

  20. Structure, chain conformation, and immunomodulatory activity of the polysaccharide purified from Bacillus Calmette Guerin formulation.

    Science.gov (United States)

    Liu, Wei; Wang, Hong; Yu, Juping; Liu, Yameng; Lu, Weisheng; Chai, Yin; Liu, Chao; Pan, Chun; Yao, Wenbing; Gao, Xiangdong

    2016-10-01

    A polysaccharide, coded as BDP, purified from the injection powder of Bacillus Calmette Guerin (BCG) polysaccharide and nucleic acid, was composed mainly of α-D-(1→4)-linked glucan with (1→6)-linked branches and trace amounts of fucose and mannose from the results of FT-IR, HPAEC-PAD and NMR spectrum. The Mw, Mn, Mz, and [Formula: see text] were determined to be 1.320×10(5)g/mol, 1.012×10(5)g/mol, 2.139×10(5)g/mol, and 21.8±3.2%nm by using HPSEC-MALLS, respectively. The ν value from [Formula: see text] was calculated to be 0.52±0.01, which firstly clarified that BDP existed as random coils in 0.9% NaCl aqueous solution. AFM and SEM combined with Congo-red test also revealed that the polysaccharide was irregular globular like or curly structure. Furthermore, in vitro tests on RAW264.7 murine macrophages cells revealed that BDP exhibited significant immunomodulatory activity. PMID:27312624

  1. 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.

  2. 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.

  3. BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6

    OpenAIRE

    Tobiume, Makoto; Shinohara, Tsutomu; Kuno, Takahira; Mukai, Shinji; Naruse, Keishi; Hatakeyama, Nobuo; OGUSHI, FUMITAKA

    2014-01-01

    Background Pneumonitis is a rare complication of bacillus Calmette-Guerin (BCG) immunotherapy seen in patients with urothelial cancer following the repeated administration of BCG. However, no case of BCG-induced pleurisy has been reported. Case presentation We here report the first case of pneumonitis with lymphocytic pleurisy following bacillus Calmette-Guerin (BCG) immunotherapy. Although marked T helper cell alveolitis was found by bronchoalveolar lavage and transbronchial biopsies, no aci...

  4. Interferon-γ Added During Bacillus Calmette-Guerin Induced Dendritic Cell Maturation Stimulates Potent Th1 Immune Responses

    Directory of Open Access Journals (Sweden)

    Pestano Linda A

    2003-10-01

    Full Text Available Abstract Dendritic cells (DC are increasingly prepared in vitro for use in immunotherapy trials. Mature DC express high levels of surface molecules needed for T cell activation and are superior at antigen-presentation than immature DC. Bacillus Calmette-Guerin (BCG is one of several products known to induce DC maturation, and interferon (IFN-γ has been shown to enhance the activity of DC stimulated with certain maturation factors. In this study, we investigated the use of IFN-γ in combination with the powerful maturation agent, BCG. The treatment of immature DC with IFN-γ plus BCG led to the upregulation of CD54, CD80, and CD86 in comparison with BCG treatment alone. In MLR or recall immune responses, the addition of IFN-γ at the time of BCG-treatment did not increase the number of antigen-specific T cells but enhanced the development of IFN-γ-producing Th1 cells. In primary immune responses, on the other hand, BCG and IFN-γ co-treated DC stimulated higher proportions of specific T cells as well as IFN-γ secretion by these T cells. Thus the use of IFN-γ during BCG-induced DC maturation differentially affects the nature of recall versus naïve antigen-specific T-cell responses. IFN-γ co-treatment with BCG was found to induce IL-12 and, in some instances, inhibit IL-10 secretion by DC. These findings greatly enhance the potential of BCG-matured dendritic cells for use in cancer immunotherapy.

  5. 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.

  6. "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.

  7. Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    Hua Wang; Wei Wei; Yu-Xian Shen; Chen Dong; Ling-Ling Zhang; Ni-Ping Wang; Li Yue; Shu-Yun Xu

    2004-01-01

    AIM: To investigate the effects and mechanisms of melatonin on immunological liver injury in mice.METHODS: A model of liver injury was induced by tail veininjection of Bacillus Calmette Guerin (BCG) and lipopolysaccharide(LPS) in mice. Kupffer cells and hepatocytes were isolatedand cultured according to a modified two-step collagenaseperfusion technique. Levels of alanine aminotransferase(ALT), aspartate aminotransferase (AST) and nitric oxide(NO), content of malondiadehyde (MDA), activity of superoxidedismutase (SOD), were measured by biochemical methods.Tumor necrosis factor-α (TNF-α) activity was determinedby RIA. Interleukin (IL)-1 activity was measured by thymocyte proliferation bioassay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a lightmicroscope.RESULTS: Immunological liver injury induced by BCG+LPSwas successfully duplicated. Serum transaminase (ALT,AST) activities were significantly decreased by melatonin(0.25, 1.0, 4.0 mg/kg bm). Meanwhile, MDA content was decreased and SOD in liver homogenates was upregulated.Furthermore, pro-inflammatory mediators (TNF-α, IL-1, NO)in serum and liver homogenates were significantly reduced by melatonin. Histological examination demonstrated that melatonin could attenuate the area and extent of necrosis,reduce the immigration of inflammatory cells. In in vitro experiment, TNF-α was inhibited at the concentrations of10-8-10-6 mol/L of melatonin, while IL-1 production of Kupffer cells induced by LPS (5 μg/mL) was decreased only at theconcentration of 10-6 mol/L of melatonin, but no effect onNO production was observed. Immunological liver injury model in vitro was established by incubating hepatocyteswith BCG- and LPS-induced Kupffer cells. Activities of ALT,TNF-α, IL-1, and MDA in supernatant were significantlyincreased. Melatonin had little effect on the level of ALT,but reduced the content of TNF-α and MDA at concentrationsof 10-7-10-5 mol/L and decreased the content of IL-1

  8. A novel recombinant Mycobacterium bovis bacillus Calmette-Guerin strain expressing human granulocyte macrophage colony-stimulating factor and Mycobacterium tuberculosis early secretory antigenic target 6 complex augments Th1 immunity

    Institute of Scientific and Technical Information of China (English)

    Xiaoling Yang; Lang Bao; Yihao Deng

    2011-01-01

    Since Mycobacterium bovis bacillus Calmette-Guerin strain (BCG) fails to protect adults from pulmonary tuberculosis (TB), there is an urgent need for developing a new vaccine. In this study, we constructed a novel recombinant BCG strain (rBCG) expressing human granulocyte macrophage colony-stimulating factor (GM-CSF) and the 6 kDa early secretory antigenic target (ESAT6) of Mycobacteriutn tuberculosis, named rBCG:GE (expressing GMCSFESAT6 complex), and evaluated the immunogenicity of the construct in BALB/c mice. Our results indicated that the rBCG:GE was able to induce higher titer of antibody than the conventional BCG, the rBCG:G (expressing GM-CSF)and the rBCG:E (expressing ESAT6). Moreover, the rBCG:GE also elicited a longer-lasting and stronger Thl cellular immune responses than the other groups, which was confirmed by the incremental proliferation of splenocytes, the increased percentages of CD4+ and CD8+ T cells of spleen, the elevated level of interferon-γ in splenocyte culture after tuberculin-purified protein derivative stimulation, and the increased concentration of GM-CSF in serum. The data presented here suggested the possibility that the recombinant BCG:GE might be a good vaccine candidate to TB.

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

    NARCIS (Netherlands)

    Buffen, K.; Oosting, M.; Quintin, J.; Ng, A.; Kleinnijenhuis, J.; Kumar, V.; Vosse, E. van de; Wijmenga, C.; Crevel, R. van; Oosterwijk, E.; Grotenhuis, A.J.; Vermeulen, S.; Kiemeney, L.A.L.M.; Veerdonk, F.L. van de; Chamilos, G.; Xavier, R.J.; Meer, J.W.M. van der; Netea, M.G.; Joosten, L.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. 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.

  11. Corynebacterium parvum- and Mycobacterium bovis bacillus Calmette-Guerin-induced granuloma formation is inhibited in TNF receptor I (TNF-RI) knockout mice and by treatment with soluble TNF-RI.

    Science.gov (United States)

    Senaldi, G; Yin, S; Shaklee, C L; Piguet, P F; Mak, T W; Ulich, T R

    1996-12-01

    The aim of this study was to examine the role of TNF receptor I (TNF-RI) in the pathogenesis of heat-killed Corynebacterium parvum- and live bacillus Calmette-Guerin (BCG)-induced granulomas. Granuloma formation was analyzed in TNF-RI knockout mice and after treatment with soluble TNF-RI (sTNF-RI). TNF-RI knockout mice injected with C. parvum or BCG developed fewer and smaller granulomas than wild-type control mice. Mice treated with sTNF-RI from days 7 to 13 after injection of C. parvum or BCG developed fewer and smaller granulomas than saline-treated control mice. Established granulomas regressed in rats treated with sTNF-RI from days 10 to 13 after injection of C. parvum. In conclusion, TNF signaling via TNF-RI contributes to the pathogenesis of C. parvum- and BCG-induced granulomas. sTNF-RI inhibits the development of granulomas and can cause the regression of established granulomas. PMID:8943410

  12. Pretreatment With Inactivated Bacillus Calmette-Guerin Increases CD4+CD25+ Regulatory T Cell Function and Decreases Functional and Structural Effects of Asthma Induction in a Rat Asthma Model.

    Science.gov (United States)

    Gong, Ping; Li, Yun; Tan, Yu-Pin; Li, Hong

    2016-04-01

    Bacillus Calmette-Guerin (BCG) has been shown to have therapeutic effects on asthma through CD4+CD25+ regulatory T cells (Tregs). We sought to assess pretreatment with inactivated BCG on CD4+CD25+ Tregs and its functional and structural effects in rat asthma model. The rat asthma model was established using ovalbumin (OVA) sensitization and challenge. Ten rats were pretreated with BCG prior to OVA and received continued BCG injections during OVA challenge (BCG+OVA group), 10 rats were treated with OVA alone (OVA group), and 10 rats were treated with saline (control group). After 9 weeks, histamine dihydrochloride effect on airway resistance was measured. Number of CD4+CD25+ Tregs was measured by flow cytometry, expression of Foxp3 and CTLA-4 mRNA was measured, and serum TGF-β levels were determined. Differential cell count in bronchoalveolar lavage fluid (BALF) was determined, and lung tissue was processed and stained with hematoxylin and eosin, Masson's trichrome, and alcine blue and periodic acid Schiff's reaction to evaluate inflammatory cell infiltration, collagen deposition, and presence of goblet cells, respectively. BCG treatment led to an increase in CD4+CD25+ Tregs, as well as an increase in Foxp3 and CTLA-4 expression and serum TGF-β levels. In addition, we observed a decrease in histamine dihydrochloride-induced airway resistance, a decrease in inflammatory leukocytes in BALF, and a decrease in airway remodeling indicators in BCG+OVA-treated rats compared with OVA-treated rats. Intradermally injected inactivated BCG has the potential to improve airway inflammation, airway resistance, and airway remodeling through a mechanism that may involve CD4+CD25+ Tregs. PMID:26495900

  13. Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis induces robust antigen-specific immune responses in mice.

    Science.gov (United States)

    Li, Wu; Li, Min; Deng, Guangcun; Zhao, Liping; Liu, Xiaoming; Wang, Yujiong

    2015-08-01

    Tuberculosis (TB) remains to be a prevalent health issue worldwide. At present, Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the singular anti-TB vaccine available for the prevention of disease in humans; however, this vaccine only provides limited protection against Mycobacterium tuberculosis (Mtb) infection. Therefore, the development of alternative vaccines and strategies for increasing the efficacy of vaccination against TB are urgently required. The present study aimed to evaluate the ability of a recombinant adenoviral vector (Ad5-CEAB) co-expressing 10-kDa culture filtrate protein, 6-kDa early-secreted antigenic target, antigen 85 (Ag85)A and Ag85B of Mtb to boost immune responses following primary vaccination with BCG in mice. The mice were first subcutaneously primed with BCG and boosted with two doses of Ad5-CEAB via an intranasal route. The immunological effects of Ad5-CEAB boosted mice primed with BCG were then evaluated using a series of immunological indexes. The results demonstrated that the prime-boost strategy induced a potent antigen-specific immune response, which was primarily characterized by an enhanced T cell response and increased production of cytokines, including interferon-γ, tumor necrosis factor-α and interleukin-2, in mice. In addition, this vaccination strategy was demonstrated to have an elevated humoral response with increased concentrations of antigen-specific bronchoalveolar lavage secretory immunoglobulin (Ig)A and serum IgG in mice compared with those primed with BCG alone. These data suggested that the regimen of subcutaneous BCG prime and mucosal Ad5-CEAB boost was a novel strategy for inducing a broad range of antigen-specific immune responses to Mtb antigens in vivo, which may provide a promising strategy for further development of adenoviral-based vaccine against Mtb infection.

  14. Investigation of the quality of Bacillus Calmette-Guerin vaccination and its related factors in 1533 infants%1533名婴幼儿卡介苗接种质量及其相关影响因素研究

    Institute of Scientific and Technical Information of China (English)

    时文明; 史太平; 朋文佳; 顾昕

    2016-01-01

    Objective:To investigate the vaccination quality of Bacillus Calmette-Guerin ( BCG ) in infants, analyze its related impacting factors and improve the effects of vaccination. Methods:The results of tuberculin( PPD) test in 1533 infants vaccinated with BCG and its related factors from Institute of Preventive Vaccination of Changzhou were analyzed,which was used to evaluate the quality of BCG vaccination. Results:The BCG scar rate and PPD positive rate were 94. 59% and 96. 09%,respectively. The differences of PPD positive rate in different gender,household register,birthweight and age were not statistically significant(P>0. 05). The PPD positive rates in infants with 3 to 5 mm or more than 5 mm of BCG scar diameter were significantly higher than that in infants with less than 3 mm of BCG scar diameter(P 0.05).卡痕均径3~5 mm和>5 mm的婴幼儿PPD试验阳转率均明显高于卡痕<3 mm者(P<0.01).结论:常州市结核病防治研究所BCG接种质量较好,达到国家基础免疫标准.性别、户籍地、出生体质量、PPD试验年龄对BCG阳转率均无明显影响,重视BCG质量和BCG接种技术对提高接种效果作用显著.

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

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    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. Bacillus calmette-guerin infection in NADPH oxidase deficiency: defective mycobacterial sequestration and granuloma formation.

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    Christine Deffert

    2014-09-01

    Full Text Available Patients with chronic granulomatous disease (CGD lack generation of reactive oxygen species (ROS through the phagocyte NADPH oxidase NOX2. CGD is an immune deficiency that leads to frequent infections with certain pathogens; this is well documented for S. aureus and A. fumigatus, but less clear for mycobacteria. We therefore performed an extensive literature search which yielded 297 cases of CGD patients with mycobacterial infections; M. bovis BCG was most commonly described (74%. The relationship between NOX2 deficiency and BCG infection however has never been studied in a mouse model. We therefore investigated BCG infection in three different mouse models of CGD: Ncf1 mutants in two different genetic backgrounds and Cybb knock-out mice. In addition, we investigated a macrophage-specific rescue (transgenic expression of Ncf1 under the control of the CD68 promoter. Wild-type mice did not develop severe disease upon BCG injection. In contrast, all three types of CGD mice were highly susceptible to BCG, as witnessed by a severe weight loss, development of hemorrhagic pneumonia, and a high mortality (∼ 50%. Rescue of NOX2 activity in macrophages restored BCG resistance, similar as seen in wild-type mice. Granulomas from mycobacteria-infected wild-type mice generated ROS, while granulomas from CGD mice did not. Bacterial load in CGD mice was only moderately increased, suggesting that it was not crucial for the observed phenotype. CGD mice responded with massively enhanced cytokine release (TNF-α, IFN-γ, IL-17 and IL-12 early after BCG infection, which might account for severity of the disease. Finally, in wild-type mice, macrophages formed clusters and restricted mycobacteria to granulomas, while macrophages and mycobacteria were diffusely distributed in lung tissue from CGD mice. Our results demonstrate that lack of the NADPH oxidase leads to a markedly increased severity of BCG infection through mechanisms including increased cytokine

  17. 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.

  18. The potential for transmission of BCG from orally vaccinated white-tailed deer (Odocoileus virginianus to cattle (Bos taurus through a contaminated environment: experimental findings.

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    Pauline Nol

    Full Text Available White-tailed deer (Odocoileus virginianus experimentally infected with a virulent strain of Mycobacterium bovis have been shown to transmit the bacterium to other deer and cattle (Bos taurus by sharing of pen waste and feed. The risk of transmission of M. bovis bacille Calmette-Guerin (BCG vaccine from orally vaccinated white-tailed deer to other deer and cattle, however, is not well understood. In order to evaluate this risk, we orally vaccinated 14 white-tailed deer with 1×10(9 colony forming units BCG in lipid-formulated baits and housed them with nine non-vaccinated deer. Each day we exposed the same seven naïve cattle to pen space utilized by the deer to look for transmission between the two species. Before vaccination and every 60 days until the end of the study, we performed tuberculin skin testing on deer and cattle, as well as interferon-gamma testing in cattle, to detect cellular immune response to BCG exposure. At approximately 27 weeks all cattle and deer were euthanized and necropsied. None of the cattle converted on either caudal fold, comparative cervical tests, or interferon-gamma assay. None of the cattle were culture positive for BCG. Although there was immunological evidence that BCG transmission occurred from deer to deer, we were unable to detect immunological or microbiological evidence of transmission to cattle. This study suggests that the risk is likely to be low that BCG-vaccinated white-tailed deer would cause domestic cattle to react to the tuberculin skin test or interferon-gamma test through exposure to a BCG-contaminated environment.

  19. 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

  20. Oral vaccination of white-tailed deer (Odocoileus virginianus) with Mycobacterium bovis Bacillus Calmette-Guerin (BCG)

    Science.gov (United States)

    Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis from livestock, particularly cattle. In Michigan, USA tuberculous white-tailed deer transmit M. bovis to other deer and cattle. One approach in dealing with this wildlife reservoir is to vaccina...

  1. Mutation in alkylhydroperoxidase D gene dramatically decreases persistence of Mycobacterium bovis bacillus calmette-guerin in infected macrophage

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    Farivar Taghi

    2008-07-01

    Full Text Available Background and Objectives: Mycobacterium tuberculosis is the leading cause of death from a single bacterial species in the world and is subjected to a highly oxidative environment in its host macrophage and consequently has evolved protective mechanisms against reactive oxygen and nitrogen intermediates. Alkyl hydroperoxidase D (AhpD is a molecule from these mycobacterial defense systems that has a dual function. It not only works with Alkyl hydroperoxidase C (AhpC in mycobacterial defense system against oxidative stress but also has a role in oxidation/reduction of succinyltransferase B (SucB, dihydrolipoamide dehydrogenase (LPD and AhpC. The present study was undertaken to find out the effects of inactivation of ahpD gene in the intra-macrophage persistence of resulted BCG mutant. Materials and Methods: We did allelic exchange mutagenesis in Mycobacterium bovis BCG and evaluate the effects of this mutagenesis in intracellular persistence of wild type BCG strains and ahpD mutant ones by comparing colony forming units (CFU in infected macrophage. Results: Our findings showed that after producing allelic exchange mutagenesis in ahpD gene of M.bovis BCG a sever decrease in the CFU′s of ahpD mutant BCG strains has been observed and intracellular persistence of ahpD mutant BCG strains decreased significantly. Conclusion: Mutagenesis in ahpD gene will cause significant decrease in intracellular survival of ahpD mutant strains than wild type M.bovis BCG strains and could leads to an inefficiency in pyruvate dehydrogenase pathway and could also impair impairs mycobacterial defense system against oxidative and nitrosative stress.

  2. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

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    Bhowmick Sudipta

    2010-06-01

    Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

  3. Persistence of Mycobacterium bovis Bacillus Calmette-Guerin (BCG) in White-tailed Deer (Odocoileus virginianus) After Oral or Parenteral Vaccination

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    Mycobacterium bovis is the cause of tuberculosis in cattle and a serious zoonotic pathogen, most commonly contracted through consumption of unpasteurized dairy products. To control this zoonosis, many countries have developed bovine tuberculosis eradication programs. Although relatively successful, ...

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

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    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.

  5. Agreement between QuantiFERON(R)-TB Gold In-Tube and the tuberculin skin test and predictors of positive test results in Warao Amerindian pediatric tuberculosis contacts

    NARCIS (Netherlands)

    Verhagen, L.M.; Maes, M.; Villalba, J.A.; d'Alessandro, A.; Rodriguez, L.P.; Espana, M.F.; Hermans, P.W.M.; Waard, J.H. de

    2014-01-01

    BACKGROUND: Interferon-gamma release assays have emerged as a more specific alternative to the tuberculin skin test (TST) for detection of tuberculosis (TB) infection, especially in Bacille Calmette-Guerin (BCG) vaccinated people. We determined the prevalence of Mycobacterium tuberculosis infection

  6. Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children

    DEFF Research Database (Denmark)

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

    2012-01-01

    Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants....

  7. 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

  8. [REITER'S SYNDROME FOLLOWING INTRAVASICAL BCG THERAPY FOR UROTHELIAL CARCINOMA. SUMMARY OF CASE REPORTS OVER THE PAST 13 YEARS IN JAPAN, INCLUDING OUR CURRENT 6 CASES].

    Science.gov (United States)

    Koike, Mayumi; Natsuyama, Takao; Matsuzaki, Kanako; Yokota, Eisuke; Shiozawa, Shinji; Chiba, Kazuto; Akakura, Koichiro

    2015-10-01

    Reiter's syndrome is one of the rare complications following intravesical bovis Bacillus Calmette-Guerin (BCG) treatment. In this study we have reviewed and discussed 101 cases including our own 6 cases over the past 13 years in Japan (2000-2013). The patients comprised 70 males and 25 females (6 cases were unknown), mean age of 63.1 (range 42 - 91). Arthritis occured 4-5 days after conjunctivitis. Thirty five (55%) of 68 patients needed corticosteroid treatment to control their arthritis. HLA-B27 is known as a risk factor of Reiter's syndrome, however, positive rate was only 2.4% (n = 41). PMID:26717781

  9. 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.

  10. 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.

  11. Oral vaccination of guinea pigs with a Mycobacterium bovis bacillus Calmette-Guerin vaccine in a lipid matrix protects against aerosol infection with virulent M. bovis.

    Science.gov (United States)

    Clark, Simon; Cross, Martin L; Nadian, Allan; Vipond, Julia; Court, Pinar; Williams, Ann; Hewinson, R Glyn; Aldwell, Frank E; Chambers, Mark A

    2008-08-01

    Increased incidence of bovine tuberculosis (TB) in the United Kingdom caused by infection with Mycobacterium bovis is a cause of considerable economic loss to farmers and the government. The Eurasian badger (Meles meles) represents a wildlife source of recurrent M. bovis infections of cattle in the United Kingdom, and its vaccination against TB with M. bovis bacillus Calmette-Guérin (BCG) is an attractive disease control option. Delivery of BCG in oral bait holds the best prospect for vaccinating badgers over a wide geographical area. Using a guinea pig pulmonary challenge model, we evaluated the protective efficacy of candidate badger oral vaccines, based on broth-grown or ball-milled BCG, delivered either as aqueous suspensions or formulated in two lipids with differing fatty acid profiles (one being animal derived and the other being vegetable derived). Protection was determined in terms of increasing body weight after aerosol challenge with virulent M. bovis, reduced dissemination of M. bovis to the spleen, and, in the case of one oral formulation, restricted growth of M. bovis in the lungs. Only oral BCG formulated in lipid gave significant protection. These data point to the potential of the BCG-lipid formulation for further development as a tool for controlling tuberculosis in badgers.

  12. Effects of dietary glutamine supplementation on the body composition and protein status of early-weaned mice inoculated with Mycobacterium bovis Bacillus Calmette-Guerin.

    Science.gov (United States)

    Rogero, Marcelo Macedo; Borges, Maria Carolina; de Castro, Inar Alves; Pires, Ivanir S O; Borelli, Primavera; Tirapegui, Julio

    2011-09-01

    Glutamine, one of the most abundant amino acids found in maternal milk, favors protein anabolism. Early-weaned babies are deprived of this source of glutamine, in a period during which endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress, mainly during infections. The objective of this study was to verify the effects of dietary glutamine supplementation on the body composition and visceral protein status of early-weaned mice inoculated with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Mice were weaned early on their 14th day of life and seperated into two groups, one of which was fed a glutamine-free diet (n = 16) and the other a glutamine-supplemented diet (40 g/kg diet) (n = 16). At 21 days of age, some mice were intraperitoneally injected with BCG. Euthanasia was performed at the 28th day of age. BCG inoculation significantly reduced body weight (P glutamine supplementation resulted in a significant increase in serum IGF-1 (P = 0.019) and albumin (P = 0.025) concentration, muscle protein concentration (P = 0.035) and lipid content (P = 0.002) in the carcass. In conclusion, dietary glutamine supplementation had a positive influence on visceral protein status but did not affect body composition in early-weaned mice inoculated with BCG.

  13. Effects of Dietary Glutamine Supplementation on the Body Composition and Protein Status of Early-Weaned Mice Inoculated with Mycobacterium bovis Bacillus Calmette-Guerin

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    Ivanir S. O. Pires

    2011-08-01

    Full Text Available Glutamine, one of the most abundant amino acids found in maternal milk, favors protein anabolism. Early-weaned babies are deprived of this source of glutamine, in a period during which endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress, mainly during infections. The objective of this study was to verify the effects of dietary glutamine supplementation on the body composition and visceral protein status of early-weaned mice inoculated with Mycobacterium bovis Bacillus Calmette-Guérin (BCG. Mice were weaned early on their 14th day of life and seperated into two groups, one of which was fed a glutamine-free diet (n = 16 and the other a glutamine-supplemented diet (40 g/kg diet (n = 16. At 21 days of age, some mice were intraperitoneally injected with BCG. Euthanasia was performed at the 28th day of age. BCG inoculation significantly reduced body weight (P < 0.001, lean mass (P = 0.002, water (P = 0.006, protein (P = 0.007 and lipid content (P = 0.001 in the carcass. Dietary glutamine supplementation resulted in a significant increase in serum IGF-1 (P = 0.019 and albumin (P = 0.025 concentration, muscle protein concentration (P = 0.035 and lipid content (P = 0.002 in the carcass. In conclusion, dietary glutamine supplementation had a positive influence on visceral protein status but did not affect body composition in early-weaned mice inoculated with BCG.

  14. Polysaccharide Nucleic Acid of Bacillus Calmette Guerin Modulates Th1/Th2 Cytokine Gene Expression in Lipopolysaccharide-Induced Mastitis in Rats

    Institute of Scientific and Technical Information of China (English)

    MIAO Jin-feng; ZHANG Yuan-shu; HUANG Guo-qing; MA Hai-tian; ZOU Si-xiang; ZHU Yu-min

    2009-01-01

    The aim of this study was to evaluate, in rats, the changes in the T helper type 1 (Th 1)/Th2 radio in mammary glands after an intramammary infusion of lipopolysaccharide (LPS) and to characterize the moderating effects of the polysaecharide nucleic acid of Bacillus Calraette Guerin (BCG-PSN) on the mammary gland. In the control group, the levels of IL-2 and INF-γ, mRNA expression increased, whereas IL-4 mRNA expression decreased after LPS challenge. As a consequence, the INF-γ/IL-4 mRNA ratio was significantly higher at 3, 6, and 9 h post-infusion (PI) compared to the control value (O h; P<0.01).BCG-PSN increased mRNA expression of both INF-γ' and IL-4 before infusion of LPS. LPS challenge significantly the reduced Th1/Th2 eytokine ratio due to Th1 cytokine IFN-γ suppression and Th2 cytokine IL-4 upregulation compared with the control group. A significant reduction ofN-acety1-β-D-glucosaminidase (NAGase) was observed at 24 h PI in the BCG-PSN treatment group compared to the control group (P<0.05). Thus, it was demonstrated that level of BCG-PSN might change the Th1/Th2 ratio mainly by enhancing the Th2 immune response. This is the first report of a Th1/Th2 change induced by coliform mastitis and characterization of the effect of BCG-PSN on mammary gland inflammation. This study makes a better understanding of the mechanisms of coliform mastitis and provides a putative novel strategy for the prevention and/or treatment of mastitis.

  15. 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.

  16. 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...

  17. [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.

  18. Effect of Bacillus Calmette-Guerin on Expression of PPAR-γ in Lung Tissue of Asthmatic Mice and Its Significance%卡介苗对哮喘小鼠肺组织中PPAR-γ表达的影响及意义

    Institute of Scientific and Technical Information of China (English)

    曾晓媛; 黄信刚; 陈红梅; 陈健

    2011-01-01

    Objective: To investigate the effect of bacillus Calmette-Guerin (BCG) on the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) in the lung tissue of asthmatic mice and its significance.Methods: Thirty adult male Kunming mice were randomly divided into three groups (n=10): the control group (group A), asthmatic group (group B), BCG group (group C).The asthmatic model was established by the ovalbumin challenge method.Mice in group B were given ovalbumin and aluminum hydroxide mixture by intraperitoncal injection at 1,8,15 day.Mice were inhaled ovalbumin solution drived by compressed Atomizer for asthma once a day (every 30min) from 22 day and continuously challenged for 7 days.Mice in group C were weekly given 0.025mg BCG by intradermal injection and continuously injected for 3 times.After 4 weeks, mice were sensitized and challenged by the method as group B.Mice in group A were given normal saline solution.The bronchiole inflammatory cell infiltration, remodeling index and lung tissue histopathological were observed.Expressions of PPAR-γ in lung tissue were assayed by RT-PCR and western blotting.Results: There were obviously bronchiole remodeling response and inflammatory cell infiltration in group B, which can be inhibited by BCG.RT-PCR and western blotting showed that the expression of PPAR-γ in lung tissue was down-regulated in group B compared to that of group A (P<0.05).While the expression of PPAR-γ in lung tissue was increased in group C after BCG treatment.Conclusion: BCG reduced infiltration of inflammatory cells and inhibited the inflammatory response to prevent airway remodeling by up-regulating the expression of PPAR-γ.The study provides a new clinical application for BCG.%目的:探讨卡介苗对哮喘小鼠肺组织中PPAR-γ表达的影响及其意义.方法:30只健康雄性昆明种小鼠随机化原则分成正常对照组(A组)、哮喘模型组(B组)和卡介苗干预组(C组),每组10只.卵蛋白致敏法复制哮

  19. [Sepsis and multiple organ failure after BCG instillation in bladder cancer].

    Science.gov (United States)

    Elmer, A; Bermes, U; Drath, L; Büscher, E; Viertel, A

    2004-12-01

    Local Bacillus Calmette-Guerin (BCG) immunotherapy is an effective and widely used treatment for superficial bladder carcino-ma. Local side effects are frequent, where-as systemic side effects are rare, but more serious. Systemic BCG infection as a life-threatening complication of intravesical BCG instillation should be suspected in any patient who presents with persistent fever after BCG instillation for bladder cancer.A 62-year-old patient had been treated with 6 intravesical BCG instillations for recurrent, multifocal bladder carcinoma.4 weeks after the last instillation, he presented with fever, malaise and scleral icterus. Laboratory tests revealed abnormal li-ver function tests, panzytopenia and signs of coagulation disorder. Bone marrow biopsy and liver biopsy showed non-caseating granulomas. Systemic BCG infection was suspected and antituberculous therapy combined with steroids was started. The patient developed severe sepsis and suffered from multiple organ failure. Despite partial improvement, the course was complicated by intracranial sinus thrombosis, and the patient died two month after admission. PMID:15645554

  20. Hepatoprotective Effects of Total Triterpenoids and Total Flavonoids from Vitis vinifera L against Immunological Liver Injury in Mice

    OpenAIRE

    Tao Liu; Jun Zhao; Long Ma; Yusong Ding; Deqi Su

    2012-01-01

    Suosuo grape (the fruits of Vitis vinifera L) has been used for prevention and treatment of liver diseases in Uighur folk medicine in China besides its edible value. In this study, the hepatoprotective effects of total triterpenoids (VTT) and total flavonoids (VTF) from Suosuo grape were evaluated in Bacille-Calmette-Guerin- (BCG-) plus-lipopolysaccharide- (LPS-) induced immunological liver injury (ILI) in mice. Various dose groups (50, 150, and 300 mg/kg) of VTT and VTF alleviated the degree...

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

    Science.gov (United States)

    Hunsawong, Taweewun; Sunintaboon, Panya; Warit, Saradee; Thaisomboonsuk, Butsaya; Jarman, Richard G; Yoon, In-Kyu; Ubol, Sukathida; Fernandez, Stefan

    2015-09-01

    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. PMID:26394138

  2. 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.

  3. ADVANCING THE UNDERSTANDING OF BEHAVIORS ASSOCIATED WITH BACILLE CALMETTE GUÉRIN INFECTION USING MULTIVARIATE ANALYSIS

    OpenAIRE

    Rodriguez-Zas, Sandra L.; Nixon, Scott E.; Lawson, Marcus A.; McCusker, Robert H; Southey, Bruce R.; O’Connor, Jason C.; Dantzer, Robert; Kelley, Keith W.

    2014-01-01

    Behavioral indicators in the murine Bacille Calmette Guérin (BCG) model of inflammation have been studied individually; however, the variability of the behaviors across BCG levels and the mouse-to-mouse variation within BCG-treatment group are only partially understood. The objectives of this study were: 1) to gain a comprehensive understanding of sickness and depression-like behaviors in a BCG model of inflammation using multivariate approaches, and 2) to explore behavioral differences betwe...

  4. 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.

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

    Science.gov (United States)

    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.

  6. 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

  7. [A Case Report of Suspected Tuberculous Granuloma in the Kidney after BCG Perfusion Therapy for Urothelial Carcinoma of the Renal Pelvis].

    Science.gov (United States)

    Kobayashi, Shin; Hori, Junichi; Okazaki, Satoshi; Hashizume, Kazumi; Watanabe, Masaki; Wada, Naoki; Kita, Masafumi; Azumi, Makoto; Iwata, Tatsuya; Matsumoto, Seiji; Kakizaki, Hidehiro

    2016-01-01

    A 66-year-old male patient was referred to our hospital for bilateral renal pelvic tumors. Ureteroscopic biopsy revealed urothelial carcinoma (UC) of low grade (G1) of the renal pelvis. Renal sparing treatment with systemic chemotherapy and percutaneous tumor resection was performed. However, during subsequent follow up, a recurrent tumor was found on the left ureter. After ureteroscopic laser ablation of the tumor, Bacillus Calmette-Guerin (BCG) perfusion therapy (once a week, total 6 weeks) was performed via a single J ureteral catheter with no adverse events. Later, another recurrent recurrence was found on the right ureter, and was managed by ureteroscopic laser ablation followed by BCG perfusion therapy via a single J ureteral catheter. However, the patient developed high fever with chill from the day after initial BCG perfusion therapy on the right side. Although we started antibiotics, high fever continued. Then antituberculous drugs were administered and his condition was improved. Computed tomographic scan revealed a right renal mass 57 mm in diameter, which was consistent with tuberculous granuloma. The tuberculous granuloma persisted despite the continuation of anti-tuberculous drugs. In exceptional cases of upper tract UC such as single kidney and bilateral tumor, BCG perfusion therapy has been used as adjunctive treatment to cure or prevent UC. However, dosages and administration methods of BCG perfusion therapy for upper tract UC still remain to be standardized. Serious adverse events after BCG perfusion therapy require prompt and proper management including the use of anti-tuberculous drugs. PMID:26932332

  8. Nonclinical Development of BCG Replacement Vaccine Candidates

    OpenAIRE

    Bernd Eisele; Martin Gengenbacher; Reginald Kidd; David McCown; Sheldon Morris; Steven Derrick; David Hokey; Dominick Laddy; Rosemary Chang; Megan Fitzpatrick; Leander Grode; Kamalakannan Velmurugan; Stefan H. E. Kaufmann; John Fulkerson; Brennan, Michael J.

    2013-01-01

    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 ...

  9. 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.

  10. Penile tuberculosis following intravesical Bacille Calmette-Guérin immunotherapy

    OpenAIRE

    Chowdhury, Anadi Roy; Dey, Ranjan Kumar

    2013-01-01

    Bacille Calmette-Guérin (BCG) is an effective treatment for patients with superficial bladder cancer and bladder carcinoma in situ (CIS). It may cause side effects usually due to local and systemic inflammatory effects. We report a case of a male patient with non-invasive urothelial carcinoma of urinary bladder (Stage T1) who developed caseating granulomas on his glans penis as a complication of intravesical BCG immunotherapy. Though there are other reported cases of BCG dissemination noted i...

  11. Spinocellulært karcinom opstået ved cikatrice efter Calmette-vaccination

    DEFF Research Database (Denmark)

    Nielsen, Rikke Maria; Andersen, F.; Salskov-Iversen, Maria Luise

    2014-01-01

    Marjolin's ulcer is an aggressive squamous cell carcinoma (SCC) found in chronically inflamed skin. SCC has been reported in smallpox vaccination sites, whereas basal cell carcinomas are more common in scar after bacille Calmette-Guerin (BCG) vaccination. A 72-year-old man presented with a chronic...... ulcer at the site of his childhood BCG vaccination. At the time of examination, a 3 x 1.5 cm fleshy and secreting ulcer was found on the shoulder. Biopsy revealed SCC, and the tumour was surgically removed. In conclusion, chronic ulcers, especially those originating in chronically inflamed skin, should...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Effect of bacillus calmette-guerin on CD+4 CD+25 CDlo127 treg in asthmatic mouse%卡介苗对哮喘小鼠CD+4CD+25CDlo127Treg表达的影响

    Institute of Scientific and Technical Information of China (English)

    葛荣领; 张建华

    2011-01-01

    目的 探讨卡介苗干预对哮喘小鼠调节性T细胞(Treg)及T淋巴细胞凋亡的影响.方法 27只小鼠随机分为3组:哮喘组,干预组,对照组.哮喘组小鼠用卵清蛋白(OVA)、氢氧化铝腹腔注射致敏,OVA雾化吸入激发,干预组在致敏前BCG干预3次,对照组生理盐水代替OVA及氢氧化铝.流式细胞术检测外周血(记为培养前)及植物血凝素(PHA)刺激培养后的外周血单个核细胞中Treg的表达,Comet法检测T淋巴细胞凋亡率.结果 培养前:哮喘组与对照组比较Treg显著降低,干预组与哮喘组比较显著升高.培养后:哮喘组与对照组比较Treg显著降低,干预组与哮喘组比较显著升高.同组小鼠Treg培养前后的比较:哮喘组、干预组表达无改变,对照组表达明显升高.T淋巴细胞凋亡率,哮喘组明显低于对照组,干预组明显高于哮喘组.结论 哮喘小鼠存在Treg数量小足和分化障碍,BCG干预能促进其数量上升,并促进T淋巴细胞凋亡.%Objective To explore the effect of BCG intervention on expression of CD/ CD+4 CD+25 Treg and T lymphocyte apopto-sis in asthmatic mouse. Methods 27 mice were randomly divided into 3 groups, the asthma model group, the treatment group and the normal control group. The mice were sensitized by ovalbumin and AL( OH) 3 with intraperitoneal injection, challenged with atomization inhalation. The treatment group were treated 3 times with BCG subcutaneous injection before sensitization. The normal control group were treated with saline water taking the place of ovalbumin and AL( OH) 3. Treg in peripheral blood and PBMC were detected by flow cytome-try, PBMC were stimulated and cultured by PHA. Counted the apoptosis ratio of T lymphocyte by Comet Assay. Results In peripheral blood: Compared the asthmatic group with the control group, Treg decreased remarkably; Compared the treatment group with the asthmatic group, it increased obviously. In PBMC: Compared the asthmatic group with the

  14. The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age

    DEFF Research Database (Denmark)

    Andersen, Andreas; Roth, Adam; Jensen, Kristoffer Jarlov;

    2013-01-01

    Bacille Calmette-Guérin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment...

  15. Risk of Inflammatory Bowel Disease following Bacille Calmette-Guérin and Smallpox Vaccination

    DEFF Research Database (Denmark)

    Villumsen, Anne Marie; Jess, Tine; Sørup, Signe;

    2013-01-01

    Childhood immunology has been suggested to play a role in development of inflammatory bowel disease (IBD) based on the studies of childhood vaccinations, infections, and treatment with antibiotics. Bacille Calmette-Guérin (BCG) and smallpox vaccinations were gradually phased-out in Denmark...

  16. 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

  17. [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.

  18. Mycobacterial Brain Tuberculomas due to Bacille Calmette-Guérin Intravesical Chemotherapy for Bladder Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Vitaly Golub

    2011-01-01

    Full Text Available Bacille Calmette-Guérin (BCG immunotherapy is widely used for the treatment of superficial bladder cancer. The authors believe that the present report is one of the first to document cerebral BCG tuberculoma in a 73-year-old immunocompetent man, three years after intra-vesical BCG immunotherapy. His workup revealed no identifiable extracranial source. He responded well to treatment with rifampin, ethambutol and moxifloxacin.

  19. Immunological efficacy of Bacille Calmette-Guérin vaccina-tion in Egyptian children:case series

    Institute of Scientific and Technical Information of China (English)

    Malak Shaheen; Ashraf Madkour

    2008-01-01

    Bacille Calmette-Guérin (BCG)vaccine is one of the most widely used vaccines in children.In Egypt,it is a part of the national compulsory childhood immunization program.The most controversial aspect of BCG is the variable efficacy found in different studies.This study was to evaluate the efficacy status of the available BCG vaccine in Egypt within the last 10 years (BCG-Copenhagen).The pilot cross sectional study included 597 Egyptian children randomly selected.Their ages ranged from 6 months to 10 years old (mean_5 years,medi-an:3 years).All were assessed for history of BCG vaccine intake (primary at infancy and /or secondary at school age)and examined for the presence BCG scar.A group of the vaccinated children (62 children with BCG scar and 69 children without BCG scar)were further assessed with tuberculin skin test (TST).Preva-lence of BCG vaccine intake in the studied children was 86.9% (519 /597).Efficacy in term of BCG scar af-ter vaccination was 66.6% (346 /519).However,efficacy in term of post BCG vaccination tuberculin sensiti-zation was only 3.8% (5 /131).BCG vaccination program in Egypt seems to be widely prevalent;however, the immunological efficacy of the available strain is questionable.

  20. 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.

  1. 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.

  2. Nonclinical Development of BCG Replacement Vaccine Candidates.

    Science.gov (United States)

    Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H E; Fulkerson, John; Brennan, Michael J

    2013-01-01

    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. PMID:26343962

  3. 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

  4. 吉安市城乡儿童卡介菌纯蛋白衍生物试验结果分析%Analysis on the test results of calmette- guerin bacillus ppd among the children in urban and rural of Jian

    Institute of Scientific and Technical Information of China (English)

    黄光明; 刘晓东; 罗智勇

    2011-01-01

    目的 了解卡介苗的接种质量,分析影响因素,为改善预防接种工作提供依据.方法 应用卡介菌纯蛋白衍生物( BCG- PPD)试验方法,随机抽取城市和乡村各250名3个月~1岁儿童,接种卡介苗3个月后进行PPD阳转率调查.结果BCG- PPD试验总阳性率88.60%,无性别差异,城市儿童BCG- PPD试验阳性率高于农村儿童.BCG-PPD试验阳性率与卡疤大小呈正相关.结论 我市儿童卡介苗接种质量较高,应改善农村预防接种条件,加强对BCG预防接种人员特别是农村预防接种人员的技术培训,有利于提高预防接种质量.%Objective To understand the quality of BCG vaccination, analysis influence factors, and provide basis for improving the vaccination work. Method Application of BCG purified protein derivative ( BCG - PPD ) test method, random selected 250 children of 3 months to 1 years old among each city and countryside, after 3 months, investigation the ppd seroconversion rate. Results The total positive rate of BCG - PPD test was 88. 60% , no sex differences, the positive rate of city children were higher than rural children. BCG - PPD test positive rate and card scar size showed positive correlation. Conclusions The BCG vaccination quality was high in our city, but we should improve rural preventive inoculation conditions, strengthen technical training of BCG vaccination staff especially rural vaccination staff, it profit for improving the quality of vaccination.

  5. 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...... 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...

  6. High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-γ release assay among HIV-infected individuals in BCG-vaccinated area

    Directory of Open Access Journals (Sweden)

    Jiang Weimin

    2009-05-01

    Full Text Available Abstract Background An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT-based IFN-γ release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-γ release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-γ response. Tuberculin skin test (TST was performed for all recruited subjects. Results The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32, group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46 and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22. In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST P 85% in patients with TB treatment for less than 1 month and CD4+ T cells ≥200/μl, while for patients treated for more than 3 months and CD4+ T cells Conclusion ELISPOT-based IFN-γ release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.

  7. 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

    INTRODUCTION: Bacille Calmette-Guérin (BCG) vaccine has beneficial non-specific effects on overall survival. After BCG vaccination, positive PPD response and scar formation are associated with increased survival. During a trial randomising low-birth-weight neonates to BCG at birth or the usual...... delayed BCG, the manufacturer of the BCG vaccine experienced a period with relatively slow growth rate of the BCG. We investigated the association between growth rate of BCG when manufacturing the vaccine and its capability to induce immune responses in vivo and in vitro. METHODS: 1633 neonates were...... in the production of BCG vaccine may influence important immunological effects of the vaccine. TRIAL REGISTRATION: clinicaltrials.gov (NCT00625482)....

  8. Characterization of soluble fibronectin binding to Bacille Calmette-Guérin.

    Science.gov (United States)

    Aslanzadeh, J; Brown, E J; Quillin, S P; Ritchey, J K; Ratliff, T L

    1989-10-01

    Fibronectin (FN), a 420 kDa glycoprotein, consists of two similar subunits linked by a disulphide bond near the C-terminal end. FN is present in soluble and matrix forms in various body fluids and tissues and has been shown to bind to variety of organisms. We characterized the conditions required for 125I-FN binding to Bacille Calmette-Guérin (BCG). The binding was dose-dependent, reached saturation within 3 min, and was essentially irreversible for at least 24 h under optimal binding conditions at pH 6.0. In contrast, the binding was reversible (greater than 90% in 24 h) when the pH was increased to 10.0. Scatchard analysis of the dose-response experiments produced a straight line, suggesting the presence of a single class of FN receptor on BCG. 125I-FN binding was trypsin-sensitive, suggesting that the BCG-binding molecule is a protein. The number of FN receptors was determined to be 8000-15,000 per bacterium. 125I-FN binding was pH dependent, with maximal binding at acidic pH. 125I-FN binding was sensitive to the presence of NaCl, with 0.08 M-NaCl inhibiting binding by 85%. These data demonstrate that soluble FN binds to a trypsin-sensitive cell-surface component of BCG in an essentially irreversible manner.

  9. Demonstrating Functional Equivalence of Pilot and Production Scale Freeze-Drying of BCG

    Science.gov (United States)

    ten Have, R.; Reubsaet, K.; van Herpen, P.; Kersten, G.; Amorij, J.-P.

    2016-01-01

    Process analytical technology (PAT)-tools were used to monitor freeze-drying of Bacille Calmette-Guérin (BCG) at pilot and production scale. Among the evaluated PAT-tools, there is the novel use of the vacuum valve open/close frequency for determining the endpoint of primary drying at production scale. The duration of primary drying, the BCG survival rate, and the residual moisture content (RMC) were evaluated using two different freeze-drying protocols and were found to be independent of the freeze-dryer scale evidencing functional equivalence. The absence of an effect of the freeze-dryer scale on the process underlines the feasibility of the pilot scale freeze-dryer for further BCG freeze-drying process optimization which may be carried out using a medium without BCG. PMID:26981867

  10. Demonstrating Functional Equivalence of Pilot and Production Scale Freeze-Drying of BCG.

    Science.gov (United States)

    Ten Have, R; Reubsaet, K; van Herpen, P; Kersten, G; Amorij, J-P

    2016-01-01

    Process analytical technology (PAT)-tools were used to monitor freeze-drying of Bacille Calmette-Guérin (BCG) at pilot and production scale. Among the evaluated PAT-tools, there is the novel use of the vacuum valve open/close frequency for determining the endpoint of primary drying at production scale. The duration of primary drying, the BCG survival rate, and the residual moisture content (RMC) were evaluated using two different freeze-drying protocols and were found to be independent of the freeze-dryer scale evidencing functional equivalence. The absence of an effect of the freeze-dryer scale on the process underlines the feasibility of the pilot scale freeze-dryer for further BCG freeze-drying process optimization which may be carried out using a medium without BCG. PMID:26981867

  11. Occupational safety of BCG vaccine vaccination:risk factors and countermeasure%卡介苗接种的职业安全危险因素及对策

    Institute of Scientific and Technical Information of China (English)

    万正敏

    2012-01-01

    目的 揭示卡介苗接种过程中存在的职业安全危险因素,减少职业伤害风险.方法 观察接种卡介苗过程中的职业安全环节,引导医务人员在卡介苗接种各环节做好防护.结果 通过对接种过程的临床观察,提出可靠的防护方法,在接种过程中按照卡介苗接种流程操作,3年中无一例医务人员发生结核分枝杆菌感染.结论 只要从卡介苗的检查、使用、废弃空安瓿的处理过程中做好防护,对有利器损伤的医务人员及时采取预防治疗,可以防止感染结核病,防护措施值得推广.%OBJECTIVE To reveal the risk factors for the occupational safety of bacillus calmette-guerin (BCG) vaccine vaccination to reduce the risk of occupational hazard. METHODS The links of occupational safety were observed carefully during BCG vaccine inoculation procedure and the medical personnel were guide to make well protection for each link. RESULTS Through the clinical observation on inoculation procedure, a dependable protection method was put forward. And in the process of inoculating BCG vaccine according to the method, no medical personnels had tubercle rod bacteria infection in three years. CONCLUSION Once the protection is well made during the processes of check and use of BGC vaccine and the abandon of empty Ampoule Bottle, and the medical personnel who are injured by sharp instruments adopt a prevention treatment in time, the tuberculosis infection can be prevented and the protection measure is worth of promoting.

  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. Recombinant Adenovirus Delivery of Calreticulin-ESAT-6 Produces an Antigen-Specific Immune Response but no Protection Against a Mycobacterium Tuberculosis Challenge

    NARCIS (Netherlands)

    Esparza-Gonzalez, S. C.; Troy, A.; Troudt, J.; Loera-Arias, M. J.; Villatoro Hernandez, Julio; Torres-Lopez, E.; Ancer-Rodriguez, J.; Gutierrez-Puente, Y.; Munoz-Maldonado, G.; Saucedo-Cardenas, O.; Montes-de-Oca-Luna, R.; Izzo, A.

    2012-01-01

    Bacillus CalmetteGuerin (BCG) has failed to efficaciously control the worldwide spread of the disease. New vaccine development targets virulence antigens of Mycobacterium tuberculosis that are deleted in Mycobacterium bovis BCG. Immunization with ESAT-6 and CFP10 provides protection against M. tuber

  14. Granulomas of the Penis: a Rare Complication of Intravesical Therapy with Bacillus Calmette-Guerin

    OpenAIRE

    Sara Isabel Alcântara Lestre; Catarina Diogo Gameiro; Alexandre João; Maria João Paiva Lopes

    2011-01-01

    A imunoterapia com o Bacilo Calmette-Guérin é amplamente usada no tratamento e profilaxia da neoplasia urotelial superficial. As complicações associadas ao tratamento são comuns. Os autores relatam um caso de inflamação granulomatosa do pênis, associada à terapia intravesical com Bacilo Calmette-Guérin, com múltiplos nódulos eritematosos indolores localizados na glande. É também efetuada uma revisão da literatura. A balanopostite granulomatosa é uma complicação rara associada à imunoterapia c...

  15. 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).

  16. BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Shrot, Shai; Soudack, Michalle [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel); Tel Aviv University, Sackler School of Medicine, Tel Aviv (Israel); Barkai, Galia [Sheba Medical Center, Pediatric Infectious Diseases Unit, Safra Children' s Hospital, Tel-Hashomer (Israel); Ben-Shlush, Aviva [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel)

    2016-02-15

    When administered to an immune-compromised patient, BCG (Bacille Calmette-Guerin) can cause disseminated and life-threatening infections. To describe the imaging findings in children with primary immunodeficiency and BCG-related infections. We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography. Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment. BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency. (orig.)

  17. BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics

    International Nuclear Information System (INIS)

    When administered to an immune-compromised patient, BCG (Bacille Calmette-Guerin) can cause disseminated and life-threatening infections. To describe the imaging findings in children with primary immunodeficiency and BCG-related infections. We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography. Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment. BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency. (orig.)

  18. Is interferon-gamma the right marker for bacille Calmette-Guérin-induced immune protection? The missing link in our understanding of tuberculosis immunology.

    Science.gov (United States)

    Abebe, F

    2012-09-01

    Bacille Calmette-Guérin (BCG), developed a century ago, is the only licensed tuberculosis (TB) vaccine in use to date. The protective efficacy of BCG against TB varies with no apparent protection in some population, and mechanisms of its immune protection is poorly known, and yet BCG is the most widely used vaccine, with more than 4 billion BCG-vaccinated children globally. BCG is probably the only licensed vaccine currently in use believed to mediate immune protection through the production of interferon (IFN)-γ by CD4 T cells, which in turn activates macrophages to kill Mycobacterium tuberculosis (Mtb). Currently, a number of new TB candidate vaccines are in different phases of clinical trial. The majority of these new vaccines are either recombinant forms of BCG or prime boosters of BCG (rBCG) and their immunogenicity is tested using BCG as a benchmark by measuring specific IFN-γ produced by CD4(+) T cells as a protective immune marker. However, some recent studies that examined mechanisms of immune protection of BCG in animals and humans have reported a lack of correlation between IFN-γ production by CD4 cells and BCG-induced immune protection. These studies point to the fact that there is a missing link in our understanding of TB immunology. Conversely, there is emerging evidence that other T cell subsets (gammadelta, γδ), CD8(+) T cells and natural killer (NK) cells may play a vital role in immune protection against Mtb infection and BCG-induced immune protection. γδ T cells and NK cells, which were considered to be part of the innate immunity in the past, have been shown to develop immunological memory upon re-encounter with the same pathogen. In this paper, the controversy over the role of IFN-γ as a marker for protective immunity against TB, and emerging data on the role of γδ T cells, CD8(+) and NK cells in TB immunology, will be presented. PMID:22861360

  19. Factors predicting BCG immunization status in northern Nigeria: a behavioral-ecological perspective.

    Science.gov (United States)

    Babalola, Stella; Lawan, Umar

    2009-03-01

    This study examines the predictors of Bacille Calmette-Guérin (BCG) immunization status among infants in northern Nigeria using a behavioral-ecological model. The findings show only 37.3 percent of the children had received BCG vaccine, and reveal that BCG immunization status in northern Nigeria is influenced by multiple layers of factors, including child's characteristics, parental or household factors, community characteristics, vaccine supply and the policy environment. At the child's level, place of birth and ownership of an immunization card are the two most significant predictors. The parental and household predictors of BCG immunization status include maternal use of antenatal care, maternal knowledge about immunization, maternal exposure to child health information, social influence and paternal approval of immunization. Both the regularity of vaccine supply to the health facility and the state of residence are associated independently with BCG immunization status. These findings stress the need for interventions at multiple levels in order to increase BCG immunization status. PMID:19240190

  20. 三级监控降低卡介苗接种后异常反应发生率的探讨%THE DISCUSSION OF THREE-LEVEL MONITORING TO REDUCE THE ABNORMAL REACTION INCIDENCE RATE AFTER BCG VACCINATION

    Institute of Scientific and Technical Information of China (English)

    陈立群; 邵丽文; 江爱玉

    2012-01-01

    Objective To discuss the effect of three -level monitoring to reduce the abnormal reaction incidence rate after bacillus calmette - guerin( BCG ) vaccination. Methods A total of 4 346 cases of newborn who were born in 2009 were assigned into control group ,3 999 cases of newborn born in 2010 into experimental group. Experimental group was given three-level monitoring on response after BCG vaccination and control group was observed traditionaly after the BCG vaccinaLion. The abnormal reaction incidence rate after BCG vaccination and the parents' satisfaction of BCG vaccination work were observed. Results The abnormal reactions of experimental group occurred at a rate of 1.50 per thousand, and the control group was 3.91 per thousand, the difference was statistically significant( P < 0. 05 ). The satisfaction of parents at discharge in experimental group was 96. 17% and control group was 94. 22% ; When the babies were six months old the satisfacLion of parenLs in experimental group was 91. 42% and control group was 88.47% with a significant difference( P<0.05 ). Conclusion Implementation of the three-level monitoring reduces the abnormal reaction incidence rate after vaccination, improves the parenLs'satisfaction with BCG vaccination work.%目的 探讨三级监控降低卡介苗接种后异常反应发生率的效果.方法 以2009年出生的新生儿4 346例为对照组,2010年出生的3 999例为试验组.试验组实施卡介苗接种后反应的三级监控,对照组采用传统的卡介苗接种后的观察.观察2组卡介苗接种后异常反应发生率及家长对卡介苗接种工作满意度.结果 试验组的异常反应发生率为1.50‰,对照组发生率为3.91‰,差异有统计学意义(P>0.05).出院时家长满意度试验组为96.17%,对照组为94.22%,婴儿6个月时满意度试验组为91.42%,对照组为88.47%,差异有统计学意义(P<0.01).结论 实施三级监控降低了接种后异常反应发生率,提高了家长对卡介苗预防接种工作的满意度.

  1. A Summary of Research on Bovine Tuberculosis Vaccines%牛结核病疫苗研究概述

    Institute of Scientific and Technical Information of China (English)

    谭伟; 谢志勤; 谢芝勋

    2014-01-01

    It is almost one hundred years since the Bacille Calmette Guerin (BCG)vaccine strain were isolated by Calmette and Guerin. BCG vaccine can be used for prevention of bovine tuberculosis. Research and development of bovine tuberculosis vaccines have been continuously conducted as the currently used BCG vaccines can only provide partial protection for cattle. In this review, we will introduce bovine tuberculosis vaccines that are currently in use, and major types, challenges and future directions of candidate bovine tuberculosis vaccines that are under development.%BCG疫苗株自Calmette和Guerin俩人分离出至今已有近百年的历史。BCG疫苗可用于预防牛结核病,但对牛的保护效果不完全,所以人们仍在不断地研发新型的牛结核病疫苗。本文将介绍目前正在使用及研发的牛结核病疫苗的主要类型、面临的挑战及今后的发展方向。

  2. Protective and therapeutic efficacy of Mycobacterium smegmatis expressing HBHA-hIL12 fusion protein against Mycobacterium tuberculosis in mice.

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    Full Text Available Tuberculosis (TB remains a major worldwide health problem. The only vaccine against TB, Mycobacterium bovis Bacille Calmette-Guerin (BCG, has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease. More efficient vaccines and improved therapies are urgently needed to decrease the worldwide spread and burden of TB, and use of a viable, metabolizing mycobacteria vaccine may be a promising strategy against the disease. Here, we constructed a recombinant Mycobacterium smegmatis (rMS strain expressing a fusion protein of heparin-binding hemagglutinin (HBHA and human interleukin 12 (hIL-12. Immune responses induced by the rMS in mice and protection against Mycobacterium tuberculosis (MTB were investigated. Administration of this novel rMS enhanced Th1-type cellular responses (IFN-γ and IL-2 in mice and reduced bacterial burden in lungs as well as that achieved by BCG vaccination. Meanwhile, the bacteria load in M. tuberculosis infected mice treated with the rMS vaccine also was significantly reduced. In conclusion, the rMS strain expressing the HBHA and human IL-12 fusion protein enhanced immunogencity by improving the Th1-type response against TB, and the protective effect was equivalent to that of the conventional BCG vaccine in mice. Furthermore, it could decrease bacterial load and alleviate histopathological damage in lungs of M. tuberculosis infected mice.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Virally Activated CD8 T Cells Home to Mycobacterium bovis BCG-Induced Granulomas but Enhance Antimycobacterial Protection Only in Immunodeficient Mice▿

    OpenAIRE

    Hogan, Laura H.; Co, Dominic O; Karman, Jozsef; Heninger, Erika; Suresh, M.; Sandor, Matyas

    2006-01-01

    The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of...

  5. Vaccine approaches for bovine tuberculosis: Correlates of protection and relevance to human tuberculosis

    Science.gov (United States)

    Tuberculosis (TB), primarily due to Mycobacterium tuberculosis in humans and Mycobacterium bovis in cattle, is a classic model of the One Health Concept. M. bovis Bacillus Calmette Guerin (BCG) was first proven effective in cattle prior to use in humans. Recent experimental trials with cattle have d...

  6. Testing a molasses-based bait for oral vaccination of white-tailed deer (Odocoileus virginianus) against Mycobacterium bovis

    Science.gov (United States)

    White-tailed deer (Odocoileus virginianus) in Michigan, USA are wildlife reservoirs of bovine tuberculosis (bTB) with documented spread to cattle. In vaccine efficacy trials, Mycobacterium bovis bacillus Calmette Guerin (BCG) administered orally reduces colonization and bTB-associated lesions in whi...

  7. Identification of a novel protein antigen encoded by a Mycobacterium tuberculosis-specific RD1 region gene

    NARCIS (Netherlands)

    Ahmad, S.; Amoudy, H.A.; Thole, J.E.R.; Young, D.B.; Mustafa, A.S.

    1999-01-01

    A genomic DNA region, designated RD1, that is present in virulent and clinical strains of Mycobacterium tuberculosis and M. bovis, has been shown to be deleted in bacillus Calmette Guerin (BCG). The DNA segments corresponding to three open reading frames (ORFs: ORF-10, ORF-14 and ORF-15) of the RD1

  8. Hepatoprotective Effects of Total Triterpenoids and Total Flavonoids from Vitis vinifera L against Immunological Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2012-01-01

    Full Text Available Suosuo grape (the fruits of Vitis vinifera L has been used for prevention and treatment of liver diseases in Uighur folk medicine in China besides its edible value. In this study, the hepatoprotective effects of total triterpenoids (VTT and total flavonoids (VTF from Suosuo grape were evaluated in Bacille-Calmette-Guerin- (BCG- plus-lipopolysaccharide- (LPS- induced immunological liver injury (ILI in mice. Various dose groups (50, 150, and 300 mg/kg of VTT and VTF alleviated the degree of liver injury of ILI mice, effectively reduced the BCG/LPS-induced elevated liver index and spleen index, hepatic nitric oxide (NO, and malondialdehyde (MDA content, increased liver homogenate alanine aminotransferase (ALT and aspartate aminotransferase (AST levels, and restored hepatic superoxide dismutase (SOD activity in ILI mice. VTT and VTF also significantly inhibited intrahepatic expression of Th1 cytokines (IFN-γ and IL-2 in ILI mice and increased intrahepatic expression of Th2 cytokines (IL-4 and IL-10. Moreover, the increased Bax/Bcl-2 ratio was significantly downregulated by VTT and VTF in liver tissue of ILI mice. These results are comparable to those of biphenyl dicarboxylate (DDB, the reference hepatoprotective agent and suggest that VTT and VTF play a protective role against immunological liver injury, which may have important implications for our understanding of the immunoregulatory mechanisms of this plant.

  9. Hepatoprotective Effects of Total Triterpenoids and Total Flavonoids from Vitis vinifera L against Immunological Liver Injury in Mice.

    Science.gov (United States)

    Liu, Tao; Zhao, Jun; Ma, Long; Ding, Yusong; Su, Deqi

    2012-01-01

    Suosuo grape (the fruits of Vitis vinifera L) has been used for prevention and treatment of liver diseases in Uighur folk medicine in China besides its edible value. In this study, the hepatoprotective effects of total triterpenoids (VTT) and total flavonoids (VTF) from Suosuo grape were evaluated in Bacille-Calmette-Guerin- (BCG-) plus-lipopolysaccharide- (LPS-) induced immunological liver injury (ILI) in mice. Various dose groups (50, 150, and 300 mg/kg) of VTT and VTF alleviated the degree of liver injury of ILI mice, effectively reduced the BCG/LPS-induced elevated liver index and spleen index, hepatic nitric oxide (NO), and malondialdehyde (MDA) content, increased liver homogenate alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and restored hepatic superoxide dismutase (SOD) activity in ILI mice. VTT and VTF also significantly inhibited intrahepatic expression of Th1 cytokines (IFN-γ and IL-2) in ILI mice and increased intrahepatic expression of Th2 cytokines (IL-4 and IL-10). Moreover, the increased Bax/Bcl-2 ratio was significantly downregulated by VTT and VTF in liver tissue of ILI mice. These results are comparable to those of biphenyl dicarboxylate (DDB, the reference hepatoprotective agent) and suggest that VTT and VTF play a protective role against immunological liver injury, which may have important implications for our understanding of the immunoregulatory mechanisms of this plant.

  10. Immunization Coverage in Migrant School Children Along the Thailand-Myanmar Border.

    Science.gov (United States)

    Kaji, Aiko; Parker, Daniel M; Chu, Cindy S; Thayatkawin, Wipa; Suelaor, Jiraporn; Charatrueangrongkun, Rachai; Salathibuppha, Kloloi; Nosten, Francois H; McGready, Rose

    2016-10-01

    The objective of this project was to document and increase vaccine coverage in migrant school children on the Thailand-Myanmar border. Migrant school children (n = 12,277) were enrolled in a school-based immunization program in four Thai border districts. The children were evaluated for vaccination completion and timing, for six different vaccines: Bacille Calmette-Guerin (BCG); Oral Polio vaccine (OPV); Hepatitis B vaccine (HepB); Diphtheria, Pertussis and Tetanus vaccine (DTP); Measles Containing Vaccine or Measles, Mumps and Rubella vaccine (MMR); Tetanus and Diphtheria containing vaccine (Td). Vaccine coverage proportions for BCG, OPV3, DTP3, HepB3 and measles containing vaccine were 92.3, 85.3, 63.8, 72.2, and 90.9 % respectively. Most children were able to receive vaccines in a time appropriate manner. School-based immunization programs offer a suitable vaccine delivery mechanism for hard-to-reach populations. However, these data suggest overall low vaccine coverage in migrant populations. Further efforts toward improving appropriate vaccine coverage and methods of retaining documentation of vaccination in mobile migrant populations are necessary for improved health.

  11. Progress in tuberculosis vaccine research%结核疫苗研究进展

    Institute of Scientific and Technical Information of China (English)

    吴昊; 王浩; 于继云

    2012-01-01

    卡介苗(BCG)的免疫保护作用存在争议,多重耐药结核杆菌(MDR-TB)的出现,以及艾滋病(AIDS)的流行,导致结核病(TB)的发病率呈现回升趋势,给TB防治提出了新的挑战.因此,发展新的TB疫苗成为TB防治的迫切需要.本文综述结核疫苗研究的最新进展.%The immunoprotective effect of Bacille Calmette-Guerin (BCG) is controversial. Appearance of multi-drug resistant tubercle bacilli(MDR-TB) and prevalence of AIDS lead to an upswing of tuberculosis (TB) incidence, which poses a challenge to TB control. Therefore, the development of new TB vaccines become an urgent need for prevention and treatment of TB. This article will review the latest developments of TB vaccine research.

  12. BCG对小鼠RAW264.7巨噬细胞miR-203、miR-142-3p、miR-21表达的影响%Effect of BCG on expression of miR-203, miR-142-3p and miR-21 in mouse RAW264.7 macrophages

    Institute of Scientific and Technical Information of China (English)

    张兆波; 魏军; 汤建中; 赵志军; 张一琳; 张瑞芹; 徐广贤

    2013-01-01

    目的:检测卡介苗(Bacillus Calmette-Guerin,BCG)刺激巨噬细胞后miR-203、miR-142-3p、miR-21表达量的变化,为研究microRNA(miRNA)在巨噬细胞抗结核分枝杆菌免疫应答中的调控作用提供依据.方法:利用浓度为1.0 ×107ml-1的BCG刺激培养的小鼠RAW264.7细胞,分别在4、8、12、24小时提取细胞small RNA,并利用相应的茎环反转录引物,反转录成cDNA,同时构建成熟miR-203、miR-142-3p、miR-21的T载体,绘制标准曲线,利用Real-Time PCR检测miR-203、miR-142-3p、miR-21的表达量.结果:BCG作用RAW264.7细胞4、8、12、24小时后,miR-21表达显著性上调(10倍以上,P<0.05),miR-142-3p表达显著性下调(20倍以上,P<0.05),miR-203在4、8、12小时表达下调(3倍以上,P<0.05),24小时后表达上调(2倍以上,P<0.05).结论:BCG刺激RAW264.7巨噬细胞后,miR-203、miR-142-3p、miR-21的表达发生显著性变化,说明这些miRNA可能通过调控免疫相关基因在巨噬细胞抗结核分枝杆菌的免疫应答中发挥着重要的作用.%Objective: To detect the influence of Bacillus Calmette-Guerin (BCG) on the expression of miit-203, miR-142-3p and miR-21 in the macrophages and provide the basis to study the regulation of miRNA in the immune response of macrophages to My-cobacterium tuberculosis. Methods:Small RNA was extracted at different times after stimulated with a concentration of 1.0 × 107 ml"1 of BCG in cultured mouse RAW264. 7 cells. After using stem-loop reverse transcription primers to reverse transcribed into cDNA, the expression of miR-203, miR-142-3p and miR-21 was detected by Real-time PCR. At the same time, building the T vector of mature miR-203, miR-142-3p and miR- 21 to make the standard curve. Results:After RAW264.7 cells was treated by BCG for 4, 8, 12 and 24 h, miR-21 expression was up-regulated significantly (More than 10 times, P < 0. 05). However, miR-142-3 p was significantly down-regulated at the same time( More than 20 times, P <0. 05

  13. 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. PMID:25924766

  14. Vesical nephrogenic adenoma: an unusual presentation of a bladder tumour

    OpenAIRE

    Martínez-Sanchíz, Carlos; Martínez-Ruiz, Jesús; Anguita-Fernandez, Pedro J.; Giménez-Bachs, José M.; Atiénzar-Tobarra, Manuel; Rodríguez, Julio Antonio Virseda; Salinas-Sánchez, Antonio S

    2011-01-01

    Vesical nephrogenic adenoma is a rare, benign entity that appears most commonly in middle-aged males. Its etiology is unknown, but it has been linked to chronic irritating factors, such as infection, trauma, urological surgery, kidney stones, foreign bodies and chemical agents, such as Bacille Calmette-Guerin. We report 2 new cases with a history of transurethral resection of the bladder and the prostate and a history of prolonged voiding symptoms. In both cases, the findings of encysted tubu...

  15. 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

  16. Enhancement of vitamin A combined vitamin D supplementation on immune response to Bacille Calmette-Guérin vaccine revaccinated in Chinese infants

    Institute of Scientific and Technical Information of China (English)

    Ying Zheng; Xue-Gang Li; Qiu-Zhen Wang; Ai-Guo Ma; Ib Christian Bygbjerg; Yong-Ye Sun; Yong Li; Ming-Ci Zheng; Xi Wang

    2014-01-01

    Objective:To investigate whether there is an association between diameter of bacilleCalmette-Guérin(BCG) scars and effect of purified protein derivative(PPD) reaction and to determine whether vitaminA(VA) combined vitaminD(VD) supplementation influences the immune response toBCG revaccinated inChinese infants.Methods:A cross-section and3-month community-randomised trial was conducted.A total of5629 infants at3,6 and12 months of age inJunanCounty ofChina were examined forBCG scar formation.Then,597 revaccinated infants were randomly assigned to supplementation(n=307) and control(n=290) groups.The supplementation group were daily assigned to1500IUVA and500IUVD for3 months.Then all infants were subjected to skin test withPPD.Results:The diameter ofBCG scars was positively correlated with diameter of skin indurations ofPPD(r=0.17,P<0.05) in the5629 infants.The rate of positive response toPPD was higher in the supplementation group than in the control group (96.1% versus89.7%,P<0.05, prevalence ratio1.07,95%CI1.02-1.12).The prevalence ratio ofPPD response for the supplementation group compared with that for the control group was1.07(95%CI1.01-1.13) for the males and1.08(95%CI1.00-1.17) for the females.For the supplementation group, the males got larger tuberculin induration than the females [(0.73±0.21) cm versus(0.67±0.20) cm, P<0.05) after intervention.Conclusions:The diameter ofBCG scars was effectively correlated withPPD response, which indicatesBCG scar formation may be an useful tool to evaluate the effect of tuberculosis prevention.VA combinedVD supplementation may play an immuno-regulatory role inBCG revaccination.This may contribute to the prevention of childhood tuberculosis.

  17. ELISPOT Refinement Using Spot Morphology for Assessing Host Responses to Tuberculosis

    Directory of Open Access Journals (Sweden)

    Sally A. Sharpe

    2012-03-01

    Full Text Available Tuberculosis is a global health problem. The Mycobacterium bovis Bacille Calmette Guerin (BCG vaccine has variable efficacy (0–80% so there is a drive to develop novel vaccines. The cytokine, interferon gamma (IFNγ, is an essential component of the protective response to M. tuberculosis (M. tb infection and is also produced in response to BCG vaccination. Induction of an IFNγ response is used as a biomarker of successful vaccination in the assessment of new tuberculosis (TB vaccines. The IFNγ ELISPOT assay provides an important tool for TB research. It is used for both the diagnosis of infection (T.Spot assay, and for the evaluation of the immunogenicity of new TB vaccine candidates in human clinical trials, in the non-human primate (NHP model of TB infection studies. The ELISPOT assay captures IFNγ produced by peripheral blood mononuclear cells (PBMCs following specific stimulation, onto a membrane so individual cells can be enumerated and the frequency of responding cells determined. Hence spot forming units (SFU per 106 cells provide the traditional measure for ELISPOT assays. The discriminatory power of SFU is limited. In some situations, the number of SFU in BCG vaccinated, and unvaccinated, subjects was found to be similar, although the spots were observed to be larger in vaccinated subjects. Spot size potentially provides a measure of the quantity of cytokine produced by individual cells. The AID ELISPOT plate reader software used to determine frequency of spots also has the capability to determine the size of each spot. Consideration of spot size in combination with spot forming units was investigated in our studies of BCG immunogenicity. This additional readout was found to enhance the discriminatory power of the ELISPOT assay, and provide more information on the immune response to BCG vaccination and infection with M.tb.

  18. New tuberculosis vaccines.

    Science.gov (United States)

    Martín Montañés, Carlos; Gicquel, Brigitte

    2011-03-01

    The current tuberculosis (TB) vaccine, bacille Calmette-Guerin (BCG), is a live vaccine used worldwide, as it protects against severe forms of the disease, saving thousands of lives every year, but its efficacy against pulmonary forms of TB, responsible for transmission of the diseases, is variable. For more than 80 years now no new TB vaccines have been successfully developed. Over the last decade the effort of the scientific community has resulted in the design and construction of promising vaccine candidates. The goal is to develop a new generation of vaccines effective against respiratory forms of the disease. We will focus this review on new prophylactic vaccine candidates that aim to prevent TB diseases. Two are the main strategies used to improve the immunity conferred by the current BCG vaccine, by boosting it with new subunit vaccines, and a second strategy is focused on the construction of new more effective live vaccines, capable to replace the current BCG and to be used as prime vaccines. After rigorous preclinical studies in different animal models new TB vaccine candidates enter in clinical trials in humans. First, a small Phase I for safety followed by immunological evaluation in Phase II trials and finally evaluated in large population Phase III efficacy trials in endemic countries. At present BCG prime and boost with different subunit vaccine candidates are the more advanced assessed in Phase II. Two prime vaccines (based on recombinant BCG) have been successfully evaluated for safety in Phase I trials. A short number of live attenuated vaccines are in advance preclinical studies and the candidates ready to enter Phase I safety trials are produced under current good manufacturing practices. PMID:21420568

  19. Polymorphism in the First Intron of Interferon-Gamma Gene (+874T/A in Patients with BCG Adenitis

    Directory of Open Access Journals (Sweden)

    N Parvaneh

    2009-09-01

    Full Text Available "nBackground: Cytokines and specially interferon-gamma (IFN-g are largely responsible for the regulation of the protective im­mune response against mycobacterial infections. Several studies have clarified the importance of common variants of IFN-g gene regarding the susceptibility to tuberculosis. Bacille Calmette-Guérin (BCG vaccine that is used to prevent se­vere forms of tuberculosis could produce local and systemic side effects. In this study we hypothesized that the IFN-g (+874T/A polymorphism was associated with development of BCG adenitis."nMethods: Thirty patients with BCG adenitis (18 males and 12 females and 30 age and sex-matched healthy children, vacci­nated with BCG during the first two days of life were chosen. All the patients and controls were of Iranian Fars origin and the study was conducted from 2005 to 2007. DNA samples were obtained from 30 patients with BCG adenitis and 30 age and sex matched healthy vaccinees. Polymorphism at +874 was identified using allele specific polymerase chain reac­tion. Allele and genotype frequencies in cases and controls were compared using the χ2 test and odds ratios (OR and their 95% confidence intervals (CI were calculated."nResults: The minor allele (T frequency was significantly lower in patients with BCG adenitis compared to controls (35% vs. 55%, P= 0.02, OR= 0.441, 95% CI= 0.211-0.919. The Armitage trend test revealed a gradually increasing protection from the AA genotype through AT to TT (common odds ratio= 0.49; P= 0.037."nConclusion: Our data suggest that in an Iranian population, the IFN-g (+874T/A polymorphism is associated with develop­ment of BCG adenitis in the vaccinees.

  20. Establishment of and Effects of BPV on Experimental Allergic Encephalomyelitis in Lewis Rats.%Lewis大鼠实验性变态反应性脑脊髓炎动物模型的建立及百日咳疫苗的影响

    Institute of Scientific and Technical Information of China (English)

    朱振国; 郑荣远; 李剑敏; 韩钊

    2008-01-01

    目的 建立可靠的Lewis大鼠实验性过敏性脑脊髓炎(experimental allergic encephalomyelitis, EAE)动物模型;方法 采用Lewis大鼠脚垫皮下注射豚鼠全脊髓匀浆(spinal cords homogenate of guinea pigs, GPSCH)和含有卡介苗(bacille calmette guerin, BCG) 10mg/ml的完全福氏佐剂(complete Freund's adjuvant, CFA)诱导EAE,从临床症状评分、光镜、电镜下病理学改变对模型进行评价.结果 Lewis大鼠EAE的发病率为9/10,潜伏期为12.6±1.01天.百日咳疫苗(bordetella pertussis vaccine, BPV)可提高EAE的发病率,缩短EAE的潜伏期(P<0.05),加重其临床症状和病理改变(P<0.05).结论 GPSCH和CFA免疫Lewis大鼠建立的EAE是成功可靠的;BPV对EAE有显著的促发作用,可诱导形成超急性EAE.

  1. LPS-inducible factor(s) from activated macrophages mediates cytolysis of Naegleria fowleri amoebae

    Energy Technology Data Exchange (ETDEWEB)

    Cleary, S.F.; Marciano-Cabral, F.

    1986-03-01

    Soluble cytolytic factors of macrophage origin have previously been described with respect to their tumoricidal activity. The purpose of this study was to investigate the mechanism and possible factor(s) responsible for cytolysis of the amoeba Naegleria fowleri by activated peritoneal macrophages from B6C3F1 mice. Macrophages or conditioned medium (CM) from macrophage cultures were incubated with /sup 3/H-Uridine labeled amoebae. Percent specific release of label served as an index of cytolysis. Bacille Calmette-Guerin (BCG) and Corynebacterium parvum macrophages demonstrated significant cytolysis of amoebae at 24 h with an effector to target ratio of 10:1. Treatment of macrophages with inhibitors of RNA or protein synthesis blocked amoebicidal activity. Interposition of a 1 ..mu..m pore membrane between macrophages and amoebae inhibited killing. Inhibition in the presence of the membrane was overcome by stimulating the macrophages with LPS. CM from SPS-stimulated, but not unstimulated, cultures of activated macrophages was cytotoxic for amoebae. The activity was heat sensitive and was recovered from ammonium sulfate precipitation of the CM. Results indicate that amoebicidal activity is mediated by a protein(s) of macrophage origin induced by target cell contact or stimulation with LPS.

  2. Immunization with the cysteine proteinase Ldccys1 gene from Leishmania (Leishmania) chagasi and the recombinant Ldccys1 protein elicits protective immune responses in a murine model of visceral leishmaniasis.

    Science.gov (United States)

    Ferreira, Josie Haydée L; Gentil, Luciana Girotto; Dias, Suzana Souza; Fedeli, Carlos Eduardo C; Katz, Simone; Barbiéri, Clara Lúcia

    2008-01-30

    The gene Ldccys1 encoding a cysteine proteinase of 30 kDa from Leishmania (Leishmania) chagasi, as well as the recombinant cysteine proteinase rLdccys1, obtained by cloning and expression of the Ldccys1 gene in the pHIS vector, were used to evaluate their ability to induce immune protective responses in BALB/c mice against L. (L.) chagasi infection. Mice were immunized subcutaneously with rLdccys1 plus Bacille Calmette Guerin (BCG) or Propionibacterium acnes as adjuvants or intramuscularly with a plasmid carrying the Ldccys1 gene (Ldccys1/pcDNA3) and CpG ODN as the adjuvant, followed by a booster with rLdccys1 plus CpG ODN. Two weeks after immunization the animals were challenged with 1 x 10(7) amastigotes of L. (L.) chagasi. Both immunization protocols induced significant protection against L. (L.) chagasi infection as shown by a very low parasite load in the spleen of immunized mice compared to the non-immunized controls. However, DNA immunization was 10-fold more protective than immunization with the recombinant protein. Whereas rLdccys1 induced a significant secretion of IFN-gamma and nitric oxide (NO), animals immunized with the Ldccys1 gene increased the production of IgG2a antibodies, IFN-gamma and NO. These results indicated that protection triggered by the two immunization protocols was correlated to a predominant Th1 response.

  3. Recent advances in the development of vaccines for tuberculosis.

    Science.gov (United States)

    Ahsan, Mohamed Jawed

    2015-05-01

    Tuberculosis (Tb) continues to be a dreadful infection worldwide with nearly 1.5 million deaths in 2013. Furthermore multi/extensively drug-resistant Tb (MDR/XDR-Tb) worsens the condition. Recently approved anti-Tb drugs (bedaquiline and delamanid) have the potential to induce arrhythmia and are recommended in patients with MDR-Tb when other alternatives fail. The goal of elimination of Tb by 2050 will not be achieved without an effective new vaccine. The recent advancement in the development of Tb vaccines is the keen focus of this review. To date, Bacille Calmette Guerin (BCG) is the only licensed Tb vaccine in use, however its efficacy in pulmonary Tb is variable in adolescents and adults. There are nearly 15 vaccine candidates in various phases of clinical trials, includes five protein or adjuvant vaccines, four viral-vectored vaccines, three mycobacterial whole cell or extract vaccines, and one each of the recombinant live and the attenuated Mycobacterium tuberculosis (Mtb) vaccine. PMID:26288734

  4. 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

  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. Ten years of tuberculosis intervention in Greenland – has it prevented cases of childhood tuberculosis?

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    Emilie Birch

    2014-07-01

    Full Text Available Background: The incidence of tuberculosis (TB disease in Greenland doubled in the 1990s. To combat the increase, national TB interventions were initiated in 2000 and strengthened in 2007. Objective: To determine whether the effect of interventions could be detected, we estimated the TB disease risk among children≤15 years before and after interventions were implemented. Design: For a study cohort, we recruited all children ≤15 years of age included in the Greenlandic Civil Registration System (CRS from 1990 to 2010. The CRS identifier was used to link cohort participants with TB cases identified based on the Greenlandic National TB registry. Bacille Calmette Guerin (BCG vaccination status was identified through year of birth, as BCG was offered to newborns born either before 1991 or after 1996. Years with interventions were defined as 2000–2006 (primary interventions and 2007–2010 (intensified interventions. Risk of TB was estimated using Poisson regression. Results: The study included 35,858 children, of whom 209 had TB disease. The TB disease incidence decreased after interventions were implemented (2007–2010: IRR [incidence rate ratios] 0.62, 95% CI: 0.39–0.95, p=0.03, compared with the 1995–1999 period. The TB disease risk was inversely associated with BCG vaccination (IRR: 0.54, 95% CI: 0.41–0.72, p<0.001. Conclusions: Years with national TB interventions in Greenland, including neonate BCG vaccination, are associated with a lower TB disease incidence among children ≤15 years of age.

  7. 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.

  8. Rapid rebound of the Treg compartment in DEREG mice limits the impact of Treg depletion on mycobacterial burden, but prevents autoimmunity.

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    Luciana Berod

    Full Text Available The development of an effective vaccine against tuberculosis (Tb represents one of the major medical challenges of this century. Mycobacterium bovis Bacille Calmette-Guerin (BCG, the only vaccine available at present, is mostly effective at preventing disseminated Tb in children, but shows variable protection against pulmonary Tb, the most common form in adults. The reasons for this poor efficacy are not completely understood, but there is evidence that T regulatory cells (Tregs might be involved. Similarly, Tregs have been associated with the immunosuppression observed in patients infected with Tb and are therefore believed to play a role in pathogen persistence. Thus, Treg depletion has been postulated as a novel strategy to potentiate M. bovis BCG vaccination on one side, while on the other, employed as a therapeutic approach during chronic Tb infection. Yet since Tregs are critically involved in controlling autoimmune inflammation, elimination of Tregs may therefore also incur the danger of an excessive inflammatory immune response. Thus, understanding the dynamics and function of Tregs during mycobacterial infection is crucial to evaluate the potential of Treg depletion as a medical option. To address this, we depleted Tregs after infection with M. bovis BCG or Mycobacterium tuberculosis (Mtb using DEREG mice, which express the diphtheria toxin (DT receptor under the control of the FoxP3 locus, thereby allowing the selective depletion of FoxP3+ Tregs. Our results show that after depletion, the Treg niche is rapidly refilled by a population of DT-insensitive Tregs (diTregs and bacterial load remains unchanged. On the contrary, impaired rebound of Tregs in DEREG × FoxP3GFP mice improves pathogen burden, but is accompanied by detrimental autoimmune inflammation. Therefore, our study provides the proof-of-principle that, although a high degree of Treg depletion may contribute to the control of mycobacterial infection, it carries the risk of

  9. Effect of Early Intervention Applied to Patients with Chronic Obstructive Pulmonary Disease at Different Stages

    OpenAIRE

    Lei, W.; M-H Chen; Y-C Pan; C-Y Chen; Y-L Cai

    2014-01-01

    Objective: Early intervention in chronic obstructive pulmonary disease (COPD) includes health education, smoking cessation, pulmonary rehabilitation and enhancing immunity (administration of influenza vaccine and polysaccharide nucleic acid fraction of bacillus Calmette-Guerin [BCG-PSN]). The effect of early intervention was investigated systematically in patients with COPD at different stages. Methods: We enrolled 422 patients with COPD at different stages without symptoms and then random...

  10. Vaccination Against Tuberculosis With Whole-Cell Mycobacterial Vaccines.

    Science.gov (United States)

    Scriba, Thomas J; Kaufmann, Stefan H E; Henri Lambert, Paul; Sanicas, Melvin; Martin, Carlos; Neyrolles, Olivier

    2016-09-01

    Live attenuated and killed whole-cell vaccines (WCVs) offer promising vaccination strategies against tuberculosis. A number of WCV candidates, based on recombinant bacillus Calmette-Guerin (BCG), attenuated Mycobacterium tuberculosis, or related mycobacterial species are in various stages of preclinical or clinical development. In this review, we discuss the vaccine candidates and key factors shaping the development pathway for live and killed WCVs and provide an update on progress. PMID:27247343

  11. BCG Vaccination Induces Robust CD4+ T Cell Responses to Mycobacterium tuberculosis Complex-Specific Lipopeptides in Guinea Pigs.

    Science.gov (United States)

    Kaufmann, Eva; Spohr, Christina; Battenfeld, Sibylle; De Paepe, Diane; Holzhauser, Thomas; Balks, Elisabeth; Homolka, Susanne; Reiling, Norbert; Gilleron, Martine; Bastian, Max

    2016-03-15

    A new class of highly antigenic, MHC-II-restricted mycobacterial lipopeptides that are recognized by CD4-positive T lymphocytes of Mycobacterium tuberculosis-infected humans has recently been described. To investigate the relevance of this novel class of mycobacterial Ags in the context of experimental bacille Calmette-Guérin (BCG) vaccination, Ag-specific T cell responses to mycobacterial lipid and lipopeptide-enriched Ag preparations were analyzed in immunized guinea pigs. Lipid and lipopeptide preparations as well as complex Ag mixtures, such as tuberculin, mycobacterial lysates, and culture supernatants, all induced a similar level of T cell proliferation. The hypothesis that lipopeptide-specific T cells dominate the early BCG-induced T cell response was corroborated in restimulation assays by the observation that Ag-expanded T cells specifically responded to the lipopeptide preparation. A comparative analysis of the responses to Ag preparations from different mycobacterial species revealed that the antigenic lipopeptides are specific for strains of the M. tuberculosis complex. Their intriguing conservation in pathogenic tuberculous bacteria and the fact that these highly immunogenic Ags seem to be actively released during in vitro culture and intracellular infection prompt the urgent question about their role in the fine-tuned interplay between the pathogen and its mammalian host, in particular with regard to BCG vaccination strategies. PMID:26889044

  12. 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.

  13. Tuberculin reaction and BCG scar

    DEFF Research Database (Denmark)

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

    2015-01-01

    rate ratio (MRR) comparing children with a BCG scar with those without was 0.42 (95% CI = 0.19; 0.93). There was a similar tendency for TST positivity: MRR = 0.47 (95% CI = 0.14; 1.54). For LBW children who had both a positive TST reaction and a scar, the MRR was 0.22 (95% CI = 0.05; 0.87). For NBW...

  14. Experimental study on the efficacy of Fuganling granula on protecting against immunological hepatic injury

    Institute of Scientific and Technical Information of China (English)

    Yanli LIU; Rong LIU; Cheng ZHEN; Quanfang GUO; Liping WU; Zhaoxi DING; Yushun BI; Zhiyu LIU

    2009-01-01

    To study the efficacy of Fuganling granula (FLG复肝灵颗粒,)in treating mouse immunological hepatic injury that was caused by Bacille Calmette Guerin (BCG) and lipopolysaccharide (LPS), a total of 60 mice were adopted, among which, 50 mice were given intraperitoneal injection with BCG and LPS to establish an immunological liver injury model and then were randomly divided into 5 groups (10 mice/group): 4 groups received treatment of FGL orally at the doses of 100 mg/kg (high-dosage), 50 mg/kg (middle-dosage), 25 mg/kg (low-dosage) and bifendate orally at the dose of 80 mg/kg, respectively. One group was treated with distilled water orally. The remaining 10 mice were given distilled water intraperitoneally as the normal control group. The indices of thymus, liver and spleen, and the activities of the alanine aminotransferase (ALT), aspartate aminotransferase (AST) in the serum were detected. Compared to the normal rat, the model group's thymus index decreased significantly. The liver index and spleen index increased significantly. The activities of serum ALT and AST increased signifi-cantly (all P<0.01). Compared to the model control group, the group treated with FGL in high-dosage, middle-dosage or low-dosage can decrease the activities of ALT and AST and the group treated with FGL in high-dosage and middle-dosage can increase the thymus index significantly (P<0.01). This experiment established the immunological liver injury model successfully and found that FGL has a remarkably protective effect on this kind of immunological hepatic injury.

  15. DNA-Launched Alphavirus Replicons Encoding a Fusion of Mycobacterial Antigens Acr and Ag85B Are Immunogenic and Protective in a Murine Model of TB Infection.

    Directory of Open Access Journals (Sweden)

    Neha Dalmia

    Full Text Available There is an urgent need for effective prophylactic measures against Mycobacterium tuberculosis (Mtb infection, particularly given the highly variable efficacy of Bacille Calmette-Guerin (BCG, the only licensed vaccine against tuberculosis (TB. Most studies indicate that cell-mediated immune responses involving both CD4+ and CD8+ T cells are necessary for effective immunity against Mtb. Genetic vaccination induces humoral and cellular immune responses, including CD4+ and CD8+ T-cell responses, against a variety of bacterial, viral, parasitic and tumor antigens, and this strategy may therefore hold promise for the development of more effective TB vaccines. Novel formulations and delivery strategies to improve the immunogenicity of DNA-based vaccines have recently been evaluated, and have shown varying degrees of success. In the present study, we evaluated DNA-launched Venezuelan equine encephalitis replicons (Vrep encoding a novel fusion of the mycobacterial antigens α-crystallin (Acr and antigen 85B (Ag85B, termed Vrep-Acr/Ag85B, for their immunogenicity and protective efficacy in a murine model of pulmonary TB. Vrep-Acr/Ag85B generated antigen-specific CD4+ and CD8+ T cell responses that persisted for at least 10 wk post-immunization. Interestingly, parenterally administered Vrep-Acr/Ag85B also induced T cell responses in the lung tissues, the primary site of infection, and inhibited bacterial growth in both the lungs and spleens following aerosol challenge with Mtb. DNA-launched Vrep may, therefore, represent an effective approach to the development of gene-based vaccines against TB, particularly as components of heterologous prime-boost strategies or as BCG boosters.

  16. BCG lymphadenopathy detected in a BCG-vaccinated infant

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    A.S. Barouni

    2004-05-01

    Full Text Available Large-scale vaccination with BCG, the live attenuated strain of Mycobacterium bovis, is being adopted around the world, although sporadic complications have occurred after the procedure. Lymphadenopathy is not uncommon especially in babies under one year (0.73% of vaccinated infants, but the swelling subsides within 2 months in most cases, with no medical or surgical treatment. Brazil adopted BCG vaccination program earlier in the seventies and by 1995 more than 96% of the infant population received this immunization. We report here the occurrence of lymphadenopathy in a two-year-old child vaccinated with the Brazilian BCG strain. The diagnosis was made using a lymph node biopsy and intestinal aspirates that yielded a positive mycobacterial culture. The isolate was resistant to isoniazid, rifampicin, pyrazinamide and thiophen-2-carbonic acid hydrazide, sensitive to streptomycin, ethambutol, and p-nitrobenzoic acid, and reacted positively to cyclo-serine and negatively to niacin. The pncA gene involved in bacterial activation of pyrazinamide contains in M. bovis a point mutation that renders pyrazinamidase unable to catalyze drug activation. Therefore, this polymorphism is a good option for developing methods to differentiate M. bovis and M. tuberculosis. Taking advantage of this difference we further analyzed the isolates by single-stranded conformation polymorphism electrophoresis of DNA following PCR of the pncA gene. The isolate identity was confirmed by RFLP electrophoretic analysis of the amplified fragment following Eco065I digestion, which selectively cleaves M. tuberculosis DNA. From this result it is proposed that RFLP of pncA gene represents an alternative for differential diagnosis of M. bovis.

  17. 重组hB7-2卡介苗对人外周血免疫细胞抗膀胱肿瘤作用的实验研究%The role of recombinant bacille Calmette-Guérin expressing recombinant human B7-2 on PBMC against bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    王靖宇; 韩瑞发; 马腾骧

    2009-01-01

    目的 探讨分泌人共刺激分子B7-2的重组卡介苗(rBCG)对人外周血单个核细胞(PBMC)IFN-α表达、免疫增强及杀伤膀胱癌细胞的作用.方法 SDS-PAGE和ELISA检测rBCG的表达产物hB7-2;rBCG和野生型BCG(wBCG)分别与PBMC共同培养,以单纯PBMC为对照,在不同时段收集培养液上清,经ELISA法检测上清液中IFN-α的表达水平;将BCG激活杀伤细胞(BCG activated killer cell,BAK细胞)与人膀胱癌EJ细胞共同培养,采用乳酸脱氧酶(LDH)释放试验检测活化免疫细胞对膀胱癌细胞的杀伤作用.结果 ELISA法检测出培养上清液hB7-2含量为3.8 U/ml.rBCG诱导PBMC产生细胞因子的表达明显高于同浓度的wBCG组(P<0.05);rBCG诱导的PBMC抗癌效应高于对照组诱导的抗癌效果(P<0.05).结论 rBCG诱导人PBMC高表达IFN-α,并通过增强人PBMC细胞的作用来提高抗膀胱肿瘤作用.%Objective To investigate the expression of IFN-α of the peripheral blood monocytes (PBMC) stimulated by bacille Calmeue-Guérin (BCG) expressing recombinant human B7-2, and the antitumor effect of BCG activated killer cells(BAK). Methods Expression of human B7-2 was detected by SDS-PAGE and ELISA. Recombinant BCG and wild-type BCG were used to stimulate PBMC in different concentrations in vitro. Supernatant was collected at various time points and IFN-α was detected by an enzyme-linked immunosorbent assay (ELISA). MTT assay was used to observe the effects of recombinant BCG on proliferation of T cell, and LDH assay was used to study antitumor cytotoxicity of BAK cells. Results The concentration of human B7-2 in culture was 3.8 U/ml by ELISA. Compared with wild-type BCG, recombinant BCG can induce more IFN-α. The results of the LDH release assay showed that the anti-tumor activity of BAK cells stimulated by recombinant BCG was 2.14 fold higher than that of wild-type BCG. Conclusion The expression of IFN-α in PBMC stimulated by recombinant BCG is higher than that stimulated by wild

  18. Ulcerated lupus vulgaris at the site of Bacille Calmette-Guérin vaccination.

    Science.gov (United States)

    Singal, Archana; Sonthalia, Sidharth; Pandhi, Deepika

    2013-01-01

    We report a case of ulcerated lupus vulgaris occurring in 1.5-year-old boy at the Bacille Calmette-Guérin vaccination site within 6 months, which was diagnosed using histology and polymerase chain reaction. The lesion resolved with isoniazid and rifampicin therapy.

  19. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: BCG vaccination is recommended at birth in low-income countries, but vaccination is often delayed. Often 20-dose vials of BCG are not opened unless at least ten children are present for vaccination ("restricted vial-opening policy"). BCG coverage is usually reported as 12-month coverage......, not disclosing the delay in vaccination. Several studies show that BCG at birth lowers neonatal mortality. We assessed BCG coverage at different ages and explored reasons for delay in BCG vaccination in rural Guinea-Bissau. METHODS: Bandim Health Project (BHP) runs a health and demographic surveillance system...... 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...

  1. The future of neonatal BCG.

    Science.gov (United States)

    Odent, Michel R

    2016-06-01

    We hypothesise that neonatal BCG (Bacillus Calmette-Guérin) might be used to adapt to a new phase in the history of human births. Among most mammals, the placenta is not effective at transferring antibodies to the fetus: antibodies are transferred immediately after birth via the colostrum. Among humans (and other mammals with hemochorial placentas) the transplacental transfer of antibodies (namely IgG) is effective. In humans, foetal concentrations of IgG sub-classes approximate to maternal concentrations at 38weeks and continue to increase thereafter. These facts explain inter-species differences regarding the basic needs of neonates. Among most mammals, the early colostrum is, strictly speaking, vital. Among humans, the main questions are about the bacteriological environment in the birthing place and how familiar it is to the mother. Today, most human beings are born in unfamiliar bacteriological environments characterized by a low microbial diversity. The effects of clinical environments may be amplified by the use of antibiotics and birth by caesarean, i.e. by-passing the bacteriologically rich perineal zone. There is already an accumulation of data confirming that the maturation of a balanced Th1/Th2 immune response is affected by the mode of delivery. There is also an accumulation of epidemiological studies detecting risk factors in the perinatal period for health conditions such as type 1 diabetes (and other autoimmune diseases), atopy, autism and obesity. In such a context there are reasons to plan randomized controlled trials with long term follow-up of the effects of BCG given immediately after birth, as a modulator of Th-1/Th-2 responses. A follow-up period in the region of 6-10years would be long enough to evaluate the prevalence of several nosologically well defined diseases. These studies would be ethically acceptable, since BCG is the only infancy vaccine that has been evaluated through randomised controlled trials with long term follow

  2. 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.

  3. Sleeping Beauty and the Story of the Bacille Calmette-Guérin Vaccine.

    Science.gov (United States)

    Fletcher, Helen A

    2016-08-30

    Mycobacterium bovis BCG is the only available vaccine for protection against tuberculosis (TB). While BCG protects children from severe disease, it has little impact on pulmonary disease in adults. A recombinant BCG vaccine BCG ΔureC::hly (strain VPM1002) is in advanced clinical trials and shows promise for improved vaccine safety but little change in efficacy in animal models. A second-generation recombinant BCG vaccine with an additional deletion of the nuoG gene (BCG ΔureC::hly ΔnuoG) shows improved efficacy in a mouse model compared to that of VPM1002. BCG was first used in humans in 1921 and, like Sleeping Beauty pricked by the spinning wheel, we have slept for 100 years, showing a reluctance to invest in clinical development or in biomanufacturing capacity for TB vaccines. The advance of recombinant BCGs should awaken us from our sleep and call us to invest in new-generation TB vaccines and to protect the biomanufacture of our current BCG vaccine.

  4. Sleeping Beauty and the Story of the Bacille Calmette-Guérin Vaccine.

    Science.gov (United States)

    Fletcher, Helen A

    2016-01-01

    Mycobacterium bovis BCG is the only available vaccine for protection against tuberculosis (TB). While BCG protects children from severe disease, it has little impact on pulmonary disease in adults. A recombinant BCG vaccine BCG ΔureC::hly (strain VPM1002) is in advanced clinical trials and shows promise for improved vaccine safety but little change in efficacy in animal models. A second-generation recombinant BCG vaccine with an additional deletion of the nuoG gene (BCG ΔureC::hly ΔnuoG) shows improved efficacy in a mouse model compared to that of VPM1002. BCG was first used in humans in 1921 and, like Sleeping Beauty pricked by the spinning wheel, we have slept for 100 years, showing a reluctance to invest in clinical development or in biomanufacturing capacity for TB vaccines. The advance of recombinant BCGs should awaken us from our sleep and call us to invest in new-generation TB vaccines and to protect the biomanufacture of our current BCG vaccine. PMID:27578760

  5. Immune responses induced by a Leishmania (Leishmania amazonensis recombinant antigen in mice and lymphocytes from vaccinated subjects

    Directory of Open Access Journals (Sweden)

    Ana Paula FERNANDES

    1997-03-01

    Full Text Available In the search for Leishmania recombinant antigens that can be used as a vaccine against American Cutaneous Leishmaniasis, we identified a Leishmania (Leishmania amazonensis recombinant protein of 33 kD (Larp33 which is recognized by antibodies and peripheral blood leukocytes (PBL from subjects vaccinated with Leishvacin ®, Larp33 was expressed in Escherichia coli after cloning of a 2,2 kb Sau3A digested genomic fragment of L. (L. amazonensis into the pDS56-6 His vector. Immunoblotting analysis indicated that Larp33 corresponds to an approximately 40-kD native protein expressed in promastigotes of L.(L. amazonensis and L. (Viannia braziliensis. Northern blots of total RNA also demonstrated that the gene coding for this protein is expressed in promastigotes of the major lineages of Leishmania causing American Cutaneous Leishmaniasis. Larp33 induced partial protection in susceptible mouse strains (BALB/c and C57BL/10 against L. (L. amazonensis after vaccination using Bacille Calmette-Guerin (BCG as adjuvant. In vitro stimulation of splenocytes from BALB/c protected mice with Larp33 elicited the secretion of IL-2 and IFN-g, suggesting that a Th1 cell-mediated protective response is associated with the resistance observed in these mice. As revealed by its immunogenic and antigenic properties, this novel recombinant antigen is a suitable candidate to compose a vaccine against cutaneous leishmaniasisA resposta imune induzida por uma proteína recombinante de Leishmania (Leishmania amazonensis de 33 kD (Larp33 foi avaliada em linfócitos de indivíduos vacinados com a Leishvacin® e em camundongos através de vacinação. Larp33 foi expressa em Escherichia coli após clonagem de um fragmento genômico de L. (L. amazonensis de 2,2 kb no vetor pDS56-6His. Larp33 foi reconhecida por anticorpos IgG presentes no soro de indivíduos vacinados com Leishvacin® e induziu proliferação em linfócitos desses indivíduos em níveis comparáveis ao ant

  6. Predictors of low prevalence of latent tuberculosis infection among Egyptian health care workers at intensive care and bronchoscopy units

    Science.gov (United States)

    Hefzy, Enas Mamdouh; Wegdan, Ahmed Ashraf; Elhefny, Radwa Ahmed; Nasser, Samar Hassan

    2016-01-01

    Aim: Latent tuberculosis infections (LTBI) contain a significant reservoir for future epidemics. Screening of health care workers (HCWs) in a high-risk tuberculosis (TB) environment is an important strategy in TB control. The study aimed to assess the prevalence of LTBI among high risk Egyptian HCWs and to assess infection associated risk factors. Methods: Fifty-two HCWs who work at intensive care unit (ICU), bronchoscopy unit, and chest diseases department were tested for LTBI using both tuberculin skin test (TST) and Quantiferon TB Gold in-tube test (QFT). Risk factors for infection, knowledge of HCWs towards different aspects of TB infection and agreement between TST and QFT were also evaluated. Results: Prevalence of LTBI in this study was 13.5% by QFT and TST. It was 13.6% by TST alone and 10.3% by QFT alone. There was good concordance between both tests (Kappa=0.713). There was a statistically significant association between prevalence of LTBI and age of staff ≥30 yr (p=0.002), period of working experience (p=0.006) and working at the Bronchoscopy Unit (p=0.001). The total knowledge of HCWs towards different aspects of TB infection was generally good. Conclusion: Although the participants in the current study were among high risk HCWs, the prevalence of LTBI was low. Bacille Calmette-Guerin (BCG) vaccination, young age, short employment duration, good knowledge and a good infection control were the predictors of low risk of contracting TB at our hospitals. The risk of TB infection in resource-limited countries can be reduced with simple continuous educational and administrative infection control programmes. PMID:27777875

  7. Gene Expression, Bacteria Viability and Survivability Following Spray Drying of Mycobacterium smegmatis

    Directory of Open Access Journals (Sweden)

    Elizabeth Hunter Lauten

    2010-04-01

    Full Text Available We find that Mycobacterium smegmatis survives spray drying and retains cell viability in accelerated temperature stress (40 °C conditions with a success rate that increases with increasing thermal, osmotic, and nutrient-restriction stresses applied to the mycobacterium prior to spray drying. M.smegmatis that are spray dried during log growth phase, where they suffer little or no nutrient-reduction stress, survive for less than 7 days in the dry powder state at accelerated temperature stress conditions, whereas M. smegmatis that are spray dried during stationary phase, where cells do suffer nutrient reduction, survive for up to 14 days. M. smegmatis that are spray dried from stationary phase, subjected to accelerated temperature stress conditions, regrown to stationary phase, spray dried again, and resubmitted to this same process four consecutive times, display, on the fourth spray drying iteration, an approximate ten-fold increase in stability during accelerated temperature stress testing, surviving up to 105 days. Microarray tests revealed significant differences in genetic expression of M. smegmatis between log phase and stationary phase conditions, between naïve (non spray-dried and multiply cycled dried M. smegmatis (in log and stationary phase, and between M. smegmatis in the dry powder state following a single spray drying operation and after four consecutive spray drying operations. These differences, and other phenotypical differences, point to the carotenoid biosynthetic pathway as a probable pathway contributing to bacteria survival in the spray-dried state and suggests strategies for spray drying that may lead to significantly greater room-temperature stability of mycobacteria, including mycobacterium bovis bacille Calmette-Guerin (BCG, the current TB vaccine.

  8. Moderate exercise increases the metabolism and immune function of lymphocytes in rats.

    Science.gov (United States)

    Navarro, Francisco; Bacurau, Aline Villa Nova; Pereira, Guilherme Borges; Araújo, Ronaldo Carvalho; Almeida, Sandro Soares; Moraes, Milton Rocha; Uchida, Marco Carlos; Costa Rosa, Luis Fernando Bicudo Pereira; Navalta, James; Prestes, Jonato; Bacurau, Reury Frank Pereira

    2013-05-01

    Exercise modulates both glucose and glutamine metabolism which influences lymphocyte function. We investigated the influence of chronic moderate exercise on glucose and glutamine metabolism in lymphocytes, the associated influence on proliferation, and cytokine and immunoglobulin production. Male Wistar rats (8 weeks old) were placed in an exercise training group (N = 15, 1 h day(-1) at 60 % VO₂max, 5 days week(-1)) for 8 weeks of exercise, or a sedentary control group. Twenty-four hours following the final training session, lymphocytes were separated, and the incorporation of [U-14C]-glucose, [U-14C]-glutamine, and [2-14C]-thymidine from the supernatant was measured. The activity of glucose-6-phosphate dehydrogenase, hexokinase, and glutaminase was measured. Lymphocytes were stimulated with ConA and LPS and incubated with the Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccine and plasma IgG and IgE were measured. Glutamine metabolism increased in both T and B lymphocytes in the trained group. In the trained group, proliferative capacity increased T lymphocytes under ConA stimulation, and increased B lymphocytes with LPS. There was a significant increase in IL-2 production and decrease in IL-4 in the trained group compared with sedentary controls. IL-2R and TNFR increased in trained rats while IL-4R decreased and were more pronounced in T lymphocytes compared with B lymphocytes. In both lymphocyte subsets, exercise training significantly increased the expression of CD54+ and CD30+ cell markers. Exercise training increased plasma IgG compared with the sedentary group. In conclusion, moderate exercise training improves immune function and metabolism in T and B lymphocytes, reflecting an increased ability to respond to immune challenges. PMID:23212119

  9. 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.

  10. Sternal Osteomyelitis after Bacillus Calmette-Guérin Vaccination

    Science.gov (United States)

    Selvestravičius, Rolandas; Sučilienė, Elena; Saniukas, Kęstutis; Bobelytė, Odeta; Usonis, Vytautas

    2016-01-01

    Presented here is the case of a nine-month-old boy with the osteomyelitis of the upper area sternum caused by bacillus Calmette-Guerin (BCG), the Danish 1331 strain vaccine against tuberculosis. Upon examination, a swelling of approximately 2×3 cm diameter was observed in the upper sternal area. The mass was hard, fixed and sensitive to palpation with no local skin hyperaemia. Chest X-rays revealed a round mass anterior to the sternum, suggesting a diagnosis of osteomyelitis. A consequent sternal biopsy was performed and Mycobacterium bovis BCG was identified by a positive growth culture. PMID:27777704

  11. Immunological evaluation of a component isolated from Mycobacterium bovis BCG with a monoclonal antibody to M. bovis BCG.

    OpenAIRE

    Minden, P; Kelleher, P J; Freed, J. H.; Nielsen, L. D.; Brennan, P J; McPheron, L; McClatchy, J K

    1984-01-01

    A component of Mycobacterium bovis BCG referred to as BCG-a was isolated through the combined use of monoclonal antibody directed to BCG and affinity chromatography. Analysis of BCG-a by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a single prominent band with a molecular weight of ca. 10,000. Structural characterization of BCG-a consisting of amino acid composition and amino-terminal sequence determination was carried out. The intact BCG-a antigen was bound by neither t...

  12. Preclinical studies on a new strategy combining the Bacillus of Calmette-Guérin with plasmid DNA-based subunit vaccines against tuberculosis/Etudes précliniques sur une nouvelle stratégie de vaccination contre la tuberculose combinant le Bacille de Calmette-Guérin avec des vaccins à ADN plasmidique

    OpenAIRE

    Bruffaerts, Nicolas

    2015-01-01

    La tuberculose est une maladie contagieuse causée par les bactéries appartenant au complexe Mycobacterium tuberculosis. On estime près de neuf millions de nouveaux cas et un million de décès chaque année dans le monde. De plus, approximativement un tiers de la population mondiale est infecté de manière latente, donc à risque de développer la maladie. Le seul vaccin préventif jusqu’à présent disponible est le Bacille de Calmette-Guérin (BCG). Cependant, son efficacité contre la forme pulmonair...

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. 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...

  17. Experimental study of Ganpitiaobu Fang on immunological liver injury in mice%肝脾调补方对小鼠免疫性肝损伤的防护作用

    Institute of Scientific and Technical Information of China (English)

    阮连国; 张妍; 朱清静

    2012-01-01

    目的:观察中药肝脾调补方对小鼠免疫性肝损伤的防护作用并探讨其药理学机制.方法:采用卡介苗(BCG)+脂多糖(LPS)建立小鼠免疫性肝损伤模型,通过肝脾调补方高、中、低剂量灌胃,观察肝脾调补方对各组小鼠血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)及肝组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)水平的影响;ELISA法检测肿瘤坏死因子-α(TNF-α)的变化.结果:肝脾调补方可明显降低免疫性肝损伤小鼠血清中ALT、AST、TNF-α水平;减少肝组织匀浆的MDA含量,升高肝匀浆SOD、GSH-Px含量.结论:肝脾调补方对BCG+LPS尾静脉注射造成的小鼠免疫性肝损伤有明显的防护作用,其作用与抗脂质过氧化有关.%Objective: To study the effects of Ganpitiaobu Fang in protecting immunity hepatic injury induced by bacille calmette Guerin (BCG) and lipopolyhepatic (LPS) in mice and study on its pharmacological mechanism. Methods: The immunological liver injury rat model was produced by intraperitonealitonealinjection with BCG plus LPS. Sixty mice divied into control group , model group, low dose group, middle dose group and high dose group randomly. The levels of alanine am intransferase (ALT) , aspartate an inotransferase (AST) , tumor necrosis factor-a (TNF-α) in blood plasma and super oxide dismutase (SOD ) of liver homogenate malondialdehyde ( MDA ) , Glutathione peroxidase ( GSH-PX) of the five groups were examined. Results: Ganpitiaobu Fang significantly reduced immunological liver injury in mice by reducing serum ALT, AST, TNF-alpha level; reducing MDA content of liver homogenate and elevated SOD, GSH-PX of contents liver homogenate. Conclusion: Ganpitiaobu Fang can obviously protect immunologicalinjury to liver in rats. Its role mechanism is related with anti-lipid peroxidation.

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

    DEFF Research Database (Denmark)

    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....

  19. Evaluation of the Immune Response to Interferon Gamma Release Assay and Tuberculin Skin Test Among BCG Vaccinated Children in East of Egypt: A Cross-Sectional Study.

    Science.gov (United States)

    Beshir, Mohamed Refaat; Zidan, Alaa Ebrahim; El-Saadny, Hosam Fathi; Ramadan, Raghdaa Abdelaziz; Karam, Nehad Ahmed; Amin, Ezzat Kamel; Mohamed, Marwa Zakaria; Abdelsamad, Nahla Mohamed

    2016-04-01

    Bacille Calmette-Guérin vaccine (BCG) vaccination is used routinely in most of countries, especially developing one. The efficacy of the BCG vaccination generally decreases with time. The tuberculin skin test (TST) is a most popular diagnostic test for suspicion of tuberculosis (TB) in children till now, but it has many false positives. The interferon-gamma release assay (IGRA) is more specific than TST for detection of childhood TB, as it is more specific to Mycobacterium tuberculosis.Evaluate the interferon gamma response and TST reaction in BCG vaccinated children in east of Egypt.150 children were included in the study aged 1 month to 12 years; the collected data from the children included, full history taking, clinical examination, examination for the presence or absence of BCG scar under direct light. All the children had performed TST, IGRA.TST was done for all studied group reveal 51.3% with size of reaction <5 mm, 39.3% with size of reaction = 5 to 9 mm while 9.3% with size of reaction ≥10 mm. Mean size of reaction was 4.07 mm. Interferon gamma release assay was done for all studied group reveal 5 children (3.3%) with positive test. There was significant difference between the size of TST reaction and age (P < 0.01) with old children were more frequent to show positive reaction. Also, children with age range 1 month to 1 year were frequently have negative IGRA test, while children with age range 4 years to 12 years were frequently have positive test (P < 0.01). There was moderate agreement between IGRA and TST results (Kappa [κ] = 0.475). With high agreement between IGRA and TST results in children with absent BCG scar (κ = 1000).Therefore, Interferon gamma release assays have higher specificity and lower cross-reactions with BCG vaccination and nontuberculous Mycobacteraie than TST. PMID:27124042

  20. 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. PMID:22749596

  1. Asthmatic Children And Immunological Effects Of BCG Vaccine Key words: Asthmatic children, BCG vaccine

    International Nuclear Information System (INIS)

    A TH2 screwed immune response is known to play a crucial role in the pathogenesis of allergy, so, preventing the differentiation of TH cells. The TH2 cells are appeared as a logical therapeutic approach to atopic asthma. The purpose of TH1 study was to determine the possible role of BCG vaccine on asthma and whether a TH1 type immune response elicited by BCG immunization could suppress the allergic sensitization in childhood asthma. Seventy asthmatic patients (50 atopic and 20 non-atopic) and fifty healthy individuals were subjected to TH1 study. Tuberculin test was performed for all groups then subjects with positive tuberculin test were excluded. The BCG vaccine was given for all groups with assessment of TH1 and TH2 cytokine response by measuring total IgE, IL-4 (for TH2 response) and INF-γ (for TH1 response). Significant reduction in IgE and IL-4, and elevation in INF-γ were determined in group I (atopic asthma) following BCG vaccination. There was non-significant change observed in IgE and IL-4 levels of group II while significant reduction in IL-4 and significant increase in INF-γ was observed after BCG vaccine

  2. 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.

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

    OpenAIRE

    Lukacs, S.; B. Tschobotko; Szabo, N. A.; Andrew Symes

    2013-01-01

    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 Tra...

  4. Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer.

    Science.gov (United States)

    Takeuchi, Ario; Eto, Masatoshi; Tatsugami, Katsunori; Shiota, Masaki; Yamada, Hisakata; Kamiryo, Yoriyuki; Dejima, Takashi; Kashiwagi, Eiji; Kiyoshima, Keijiro; Inokuchi, Junichi; Takahashi, Ryosuke; Yokomizo, Akira; Ohara, Naoya; Yoshikai, Yasunobu

    2016-06-01

    Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is used for the treatment of bladder cancer. The recruitment of neutrophlis to the bladder after BCG instillation exerts anti-tumor activity against bladder tumor. We have recently demonstrated that interleukin (IL)-17A produced by γδ T cells played a role in the recruitment of neutrophlis to the bladder after BCG instillation. IL-15 is known to play an important role in neutrophil migration during inflammation. We previously constructed a recombinant BCG strain expressing the fusion protein of IL-15 and Ag85B (BCG-IL-15) for prevention of Mycobacterium tuberculosis infection. Here we compared the efficacy of the BCG-IL-15 in protection against bladder cancer with that of rBCG-Ag85B (BCG). Six-week-old female C57BL/6 mice were inoculated with MB49 bladder tumor cells in the bladder and subsequently intravesically inoculated with BCG or BCG-IL-15. BCG-IL-15 treatment significantly prolonged survival of mice inoculated with bladder cancer cells compared with BCG treatment. Infiltration of neutrophils was significantly elevated in BCGB-IL-15 treated mice accompanied by increased chemokines (MIP-2 and MIP-1α) in the bladder. Thus, BCG-IL-15 exerted additive effect on Infiltration of neutrophils in the bladder. BCG-IL-15 may be a promising drug for non-muscle invasive bladder cancer. PMID:27093372

  5. 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.

  6. TO ESTIMATE SERUM ADA LEVELS IN BCG VACCINATED CHILDREN

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    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.

  7. INTRAVESICAL BCG THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    OpenAIRE

    K. M. Figurin

    2014-01-01

    The paper considers the state-of-the-art of BCG vaccine treatment for non-muscle invasive bladder cancer. It gives data on the meta-analyses of foreign studies of the efficiency of BCG therapy in this pathology.

  8. Optimization and scale-up of cell culture and purification processes for production of an adenovirus-vectored tuberculosis vaccine candidate.

    Science.gov (United States)

    Shen, Chun Fang; Jacob, Danielle; Zhu, Tao; Bernier, Alice; Shao, Zhongqi; Yu, Xuefeng; Patel, Mehul; Lanthier, Stephane; Kamen, Amine

    2016-06-17

    Tuberculosis (TB) is the second leading cause of death by infectious disease worldwide. The only available TB vaccine is the Bacille Calmette-Guerin (BCG). However, parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. AdAg85A, an adenoviral vector expressing the mycobacterial protein Ag85A, is a new tuberculosis vaccine candidate, and has shown promising results in pre-clinical studies and phase I trial. This adenovirus vectored vaccine is produced using HEK 293 cell culture. Here we report on the optimization of cell culture conditions, scale-up of production and purification of the AdAg85A at different scales. Four commercial serum-free media were evaluated under various conditions for supporting the growth of HEK293 cell and production of AdAg85A. A culturing strategy was employed to take advantages of two culture media with respective strengths in supporting the cell growth and virus production, which enabled to maintain virus productivity at higher cell densities and resulted in more than two folds of increases in culture titer. The production of AdAg85A was successfully scaled up and validated at 60L bioreactor under the optimal conditions. The AdAg85A generated from the 3L and 60L bioreactor runs was purified through several purification steps. More than 98% of total cellular proteins was removed, over 60% of viral particles was recovered after the purification process, and purity of AdAg85A was similar to that of the ATCC VR-1516 Ad5 standard. Vaccination of mice with the purified AdAg85A demonstrated a very good level of Ag85A-specific antibody responses. The optimized production and purification conditions were transferred to a GMP facility for manufacturing of AdAg85A for generation of clinical grade material to support clinical trials. PMID:27154390

  9. 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.

  10. Enhancement of vitamin A combined vitamin D supplementation on immune response to Bacille Calmette-Guérin vaccine revaccinated in Chinese infants

    DEFF Research Database (Denmark)

    Zheng, Y; Wang, Q.Z.; Ma, Aiguo;

    2014-01-01

    The diameter of BCG scars was effectively correlated with PPD response, which indicates BCG scar formation may be an useful tool to evaluate the effect of tuberculosis prevention. VA combined VD supplementation may play an immuno-regulatory role in BCG revaccination. This may contribute to the pr...

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

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    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

  12. 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.

  13. BCG vaccination at birth and early childhood hospitalisation

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...... 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.......94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics. CONCLUSIONS: BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15...

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

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    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

  15. Mechanisms of recrudescence of Mycobacterium bovis BCG infection in mice.

    OpenAIRE

    Cox, J H; Knight, B. C.; Ivanyi, J.

    1989-01-01

    The capacity of various immunosuppressive agents to cause a recrudescence of the replication of Mycobacterium bovis BCG in the spleens of chronically infected mice was investigated. The actions of three corticosteroid preparations, cyclosporin A, and anti-T-cell subset monoclonal antibodies were compared. Treatment of mice with hydrocortisone acetate, which depressed the number of splenic lymphocytes and suppressed T-cell responses, most effectively exacerbated the stationary BCG counts, at 4...

  16. Disseminated tuberculoid lesions in infants following BCG vaccination.

    OpenAIRE

    Trevenen, C. L.; Pagtakhan, R. D.

    1982-01-01

    The records of 830 consecutive autopsies at Children's Hospital, Winnipeg revealed that 26 of the 36 infants (34 Canadian Indian, 1 Inuit and 1 Caucasian) given BCG vaccine shortly after birth had tuberculoid granulomas in various sites, including the vaccination site, regional lymph nodes, liver, spleen, lung, bone marrow and salivary gland. Mycobacterium bovis, BCG type, was identified in three of the four cases in which isolation was attempted. The principal causes of death had been sudden...

  17. 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.

  18. Manipulation of BCG vaccine: a double-edged sword.

    Science.gov (United States)

    Singh, V K; Srivastava, R; Srivastava, B S

    2016-04-01

    Mycobacterium bovis Bacillus Calmette-Guérin (BCG), an attenuated vaccine derived from M. bovis, is the only licensed vaccine against tuberculosis (TB). Despite its protection against TB in children, the protective efficacy in pulmonary TB is variable in adolescents and adults. In spite of the current knowledge of molecular biology, immunology and cell biology, infectious diseases such as TB and HIV/AIDS are still challenges for the scientific community. Genetic manipulation facilitates the construction of recombinant BCG (rBCG) vaccine that can be used as a highly immunogenic vaccine against TB with an improved safety profile, but, still, the manipulation of BCG vaccine to improve efficacy should be carefully considered, as it can bring in both favourable and unfavourable effects. The purpose of this review is not to comprehensively review the interaction between microorganisms and host cells in order to use rBCG expressing M. tuberculosis (Mtb) immunodominant antigens that are available in the public domain, but, rather, to also discuss the limitations of rBCG vaccine, expressing heterologous antigens, during manipulation that pave the way for a promising new vaccine approach. PMID:26810060

  19. 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.

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

    Science.gov (United States)

    Lukacs, S; Tschobotko, B; Szabo, N A; Symes, Andrew

    2013-01-01

    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. PMID:23844314

  1. 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.

  2. Determinants of vaccination coverage in rural Nigeria

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    Meurice Francois P

    2008-11-01

    Full Text Available Abstract Background Childhood immunization is a cost effective public health strategy. Expanded Programme on Immunisation (EPI services have been provided in a rural Nigerian community (Sabongidda-Ora, Edo State at no cost to the community since 1998 through a privately financed vaccination project (private public partnership. The objective of this survey was to assess vaccination coverage and its determinants in this rural community in Nigeria Methods A cross-sectional survey was conducted in September 2006, which included the use of interviewer-administered questionnaire to assess knowledge of mothers of children aged 12–23 months and vaccination coverage. Survey participants were selected following the World Health Organization's (WHO immunization coverage cluster survey design. Vaccination coverage was assessed by vaccination card and maternal history. A child was said to be fully immunized if he or she had received all of the following vaccines: a dose of Bacille Calmette Guerin (BCG, three doses of oral polio (OPV, three doses of diphtheria, pertussis and tetanus (DPT, three doses of hepatitis B (HB and one dose of measles by the time he or she was enrolled in the survey, i.e. between the ages of 12–23 months. Knowledge of the mothers was graded as satisfactory if mothers had at least a score of 3 out of a maximum of 5 points. Logistic regression was performed to identify determinants of full immunization status. Results Three hundred and thirty-nine mothers and 339 children (each mother had one eligible child were included in the survey. Most of the mothers (99.1% had very positive attitudes to immunization and > 55% were generally knowledgeable about symptoms of vaccine preventable diseases except for difficulty in breathing (as symptom of diphtheria. Two hundred and ninety-five mothers (87.0% had a satisfactory level of knowledge. Vaccination coverage against all the seven childhood vaccine preventable diseases was 61.9% although it

  3. 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

  4. 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.

  5. 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.

  6. Recombinant Mycobacterium bovis BCG as an HIV vaccine vector.

    Science.gov (United States)

    Chapman, Rosamund; Chege, Gerald; Shephard, Enid; Stutz, Helen; Williamson, Anna-Lise

    2010-06-01

    HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable, a necessary consideration for developing countries. In this review we discuss the numerous factors that influence generation of a genetically stable recombinant BCG vaccine for HIV. PMID:20353397

  7. Recombinant Mycobacterium bovis BCG as an HIV Vaccine Vector

    OpenAIRE

    Chapman, Rosamund; Chege, Gerald; Shephard, Enid; Stutz, Helen; Williamson, Anna-Lise

    2010-01-01

    HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addi...

  8. 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; Bjerregaard-Andersen, M;

    2016-01-01

    . 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...... children vaccinated with Russian BCG (87%), the relative risk (RR) being 1.11 (1.06-1.16). The effect was stronger in girls, and BCG scar size was larger among infants vaccinated with the Danish strain. CONCLUSION: BCG strain influences scar prevalence and scar size, and may have sex differential effects...

  9. Increased B and T Cell Responses in M. bovis Bacille Calmette-Guérin Vaccinated Pigs Co-Immunized with Plasmid DNA Encoding a Prototype Tuberculosis Antigen

    DEFF Research Database (Denmark)

    Bruffaerts, Nicolas; Pedersen, Lasse Eggers; Vandermeulen, Gaëlle;

    2015-01-01

    two regions with strong predicted SLA-1*0401/SLA-1*0801 binding affinity, was promiscuously recognized by 6/6 animals vaccinated with the BCG-pAg85A combination. Our study provides a proof of concept in a large mammalian species, for a new Th1 and CD8+ targeting tuberculosis vaccine, based on BCG...

  10. New vaccines against tuberculosis: lessons learned from BCG immunisation in Brazil.

    Science.gov (United States)

    Antas, P R Z; Castello-Branco, L R R

    2008-07-01

    The current tuberculosis (TB) vaccine Mycobacterium bovis BCG has been employed for some 70 years in Brazil and lessons from its use should be taken in account for the development or improvement of new TB vaccines. The vast majority of the current population has been vaccinated with BCG, with the possible requirement for a booster immunisation in adulthood for TB protection. BCG Moreau strain also protects against leprosy, meningitis and extrapulmonary forms of TB. Factors related to differences in strain, dosage and BCG administering protocol have been responsible for the variable efficacy of BCG. This vaccine is clearly affected by, as yet unclear, host and/or environmental variables. In this brief review, we describe some aspects of BCG immunisation observed in Brazil that may be of importance for improving or replacing BCG. PMID:18440575

  11. Revaccination of cattle with bacille Calmette-Guérin two years after first vaccination when immunity has waned, boosted protection against challenge with Mycobacterium bovis.

    Science.gov (United States)

    Parlane, Natalie A; Shu, Dairu; Subharat, Supatsak; Wedlock, D Neil; Rehm, Bernd H A; de Lisle, Geoffrey W; Buddle, Bryce M

    2014-01-01

    In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB) and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 2½ years after vaccination and to determine the effect of revaccination after 2 years. Seventy-nine calves were divided into five groups (n = 15-17 calves/group) with four of the groups vaccinated subcutaneously with 105 CFU of BCG Danish at 2-4 weeks of age and the fifth group serving as non-vaccinated controls. Three of the four BCG-vaccinated groups were revaccinated 2 years after the initial vaccination. One BCG-vaccinated group was revaccinated with BCG. A second group was vaccinated subcutaneously with a TB protein vaccine consisting of biopolyester particles (Biobeads) displaying two mycobacterial proteins, ESAT-6 and Antigen 85A, mixed with an adjuvant. A third group was vaccinated with TB proteins from M. bovis culture filtrate, mixed with an adjuvant. Twenty-three weeks after the BCG revaccination, all animals were challenged endotracheally with virulent M. bovis and a further 13 weeks later, animals were killed and necropsied to determine protection against TB. The BCG-vaccinated animals produced positive tuberculin caudal fold intradermal (15 of 62 animals) and IFN-γ TB test responses (six of 62 animals) at 6 months after vaccination, but not at subsequent time-points compared to the non-vaccinated animals. Calves receiving a single vaccination with BCG vaccine 2½ years prior to challenge were not protected against TB, while those revaccinated with BCG 2 years after the initial vaccination displayed significant reductions in lung and pulmonary lymph node lesion scores compared to the non-vaccinated animals. In contrast, no reduction in lesion scores was observed in the animals revaccinated with the TB protein vaccines with their immune

  12. Immunisation of colorectal cancer patients with autologous tumour cells

    DEFF Research Database (Denmark)

    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...... the criteria for inclusion. No serious side effects were observed. With three years of observation time, two patients are healthy, while the rest have had recurrence, and two of them have died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80...... of immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled...

  13. Antimycobacterial evaluation of novel [4,5-dihydro-1H-pyrazole-1-carbonyl]pyridine derivatives synthesized by microwave-mediated Michael addition.

    Science.gov (United States)

    Sedighi, Vida; Azerang, Parisa; Sardari, Soroush

    2015-06-01

    The focus of this study is the synthesis and biological activity evaluation of a series of dibenzalaceton derivatives (3a-3n) and novel [4,5-dihydro-1H-pyrazole-1-carbonyl]pyridine derivatives (5a-5g) against Mycobacterium bovis, Bacillus Calmette-Guerin (BCG). Dibenzalacetone derivatives were synthesized by benzaldehyde derivatives. The [4,5-dihydro-1H-pyrazole-1-carbonyl]pyridine derivatives were synthesized by Michael addition reaction and using green chemistry microwave-mediated method. All compounds were evaluated against BCG and the activity expressed as minimum inhibitory concentration (MIC) in μM. The result showed good activity for all the compounds especially compounds (3a), (3n), and (5a) illustrated high activity (7.03, 8.10 and 5.37 μM, respectively).

  14. Granulomas do pênis: uma complicação rara da terapia intravesical com Bacilo Calmette-Guérin Granulomas of the penis: a rare complication of intravesical therapy with Bacillus Calmette-Guerin

    Directory of Open Access Journals (Sweden)

    Sara Isabel Alcântara Lestre

    2011-08-01

    Full Text Available A imunoterapia com o Bacilo Calmette-Guérin é amplamente usada no tratamento e profilaxia da neoplasia urotelial superficial. As complicações associadas ao tratamento são comuns. Os autores relatam um caso de inflamação granulomatosa do pênis, associada à terapia intravesical com Bacilo Calmette-Guérin, com múltiplos nódulos eritematosos indolores localizados na glande. É também efetuada uma revisão da literatura. A balanopostite granulomatosa é uma complicação rara associada à imunoterapia com Bacilo Calmette-Guérin, com uma apresentação clinicamente heterogênea que pode dificultar o diagnóstico. O seu reconhecimento clínico é essencial para o início precoce de tuberculostáticos e interrupção de Bacilo Calmette-GuérinImmunotherapy with Bacillus Calmette-Guérin is widely used for treatment and prophylaxis of superficial urothelial cancer. Complications associated with Bacillus Calmette-Guérin treatment are common. The authors describe a case of granulomatous inflammation of the penis associated with intravesical Bacillus Calmette-Guérin therapy, presenting with multiple erythematous and painless nodules located on the glans. A review of the literature is also performed. Granulomatous balanoposthitis is a rare complication of Bacillus Calmette-Guérin immunotherapy, with heterogeneous clinical presentation, which can make the diagnosis difficult. Its clinical recognition is essential for early start of therapy with antitubercular agents and interruption of Bacillus Calmette-Guérin

  15. 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.

  16. Identification of N6,N6-Dimethyladenosine in Transfer RNA from Mycobacterium bovis Bacille Calmette-Guérin

    Directory of Open Access Journals (Sweden)

    Peter C. Dedon

    2011-06-01

    Full Text Available There are more than 100 different ribonucleoside structures incorporated as post-transcriptional modifications, mainly in tRNA and rRNA of both prokaryotes and eukaryotes, and emerging evidence suggests that these modifications function as a system in the translational control of cellular responses. However, our understanding of this system is hampered by the paucity of information about the complete set of RNA modifications present in individual organisms. To this end, we have employed a chromatography-coupled mass spectrometric approach to define the spectrum of modified ribonucleosides in microbial species, starting with Mycobacterium bovis BCG. This approach revealed a variety of ribonucleoside candidates in tRNA from BCG, of which 12 were definitively identified based on comparisons to synthetic standards and 5 were tentatively identified by exact mass comparisons to RNA modification databases. Among the ribonucleosides observed in BCG tRNA was one not previously described in tRNA, which we have now characterized as N6,N6-dimethyladenosine.

  17. 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.

  18. The Effect of Bacille Calmette-Guérin Vaccination at Birth on Tuberculin Skin Test Reactivity

    Directory of Open Access Journals (Sweden)

    I. Sedighi

    2013-10-01

    Full Text Available Introduction & Objective: The World Health Organization estimates that 1.3 million Tubercu-losis cases occur in children each year. Due to the lack of sputum examination in children, the diagnosis of pediatric tuberculosis is based on three criteria; close contact history, chest x ray finding and positive tuberculin skin test..On the other hand, BCG vaccine that in our na-tional immunization schedule, routinely administered is able to make a positive skin test. The aim of this study is to evaluate the tuberculin skin test reactions in children who have re-ceived BCG vaccine. Materials & Methods: This analytic cross sectional study was performed on 564 cases of 1-6 year old children previously vaccinated with BCG at birth and chosen by cluster sampling. Data of each child obtained for age, sex and retained BCG scar. In the second step informed parental consent was obtained then TST was administered by injecting 0.1 ml of 5 units puri-fied protein derivated (PPD into the volar surface of the forearm.The TST induration was measured 48-72 hours after injection of PPD .TST administration and measurement of indu-ration were done by trained healthcare workers. Data were analyzed with One-Way ANOVA and t-test by SPSS version14. Results: In our study, out of 564 children, 288 were male and 278 were female. 319(56.4% cases didn’t show any reaction . Out of all, 228 cases (40.6% had TST reaction 1-10mm 9 cases (1.6% had TST 10-15 mm and only 8 cases (1.4% had TST induration>15 mm . Mean indurations diameter was 2.9±1.8 mm and according to the definition of positive TST only 12 cases (2.1% had positive TST. There was no statistically sexual preference in TST reaction but with increasing of age induration diameter of TST decreased meaning that there is an inverse relationship between age and TST reaction. Conclusion: According to our results, BCG vaccination at birth did not have any major effect in tuberculin skin test and each child with positive TST

  19. Added value of use of a purified protein derivative-based enzyme-linked immunosorbent spot assay for patients with Mycobacterium bovis BCG infection after intravesical BCG instillations.

    Science.gov (United States)

    Heemstra, Karen A; Bossink, Ailko W J; Spermon, Roan; Bouwman, John J M; van der Kieft, Robert; Thijsen, Steven F T

    2012-06-01

    In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after intravesical BCG instillations for bladder carcinoma. PMID:22461529

  20. Added Value of Use of a Purified Protein Derivative-Based Enzyme-Linked Immunosorbent Spot Assay for Patients with Mycobacterium bovis BCG Infection after Intravesical BCG Instillations

    OpenAIRE

    Heemstra, Karen A.; Bossink, Ailko W. J.; Spermon, Roan; Bouwman, John J. M.; van der Kieft, Robert; Thijsen, Steven F. T.

    2012-01-01

    In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after intravesical BCG instillations for bladder carcinoma.

  1. [Comparative study of two dried intradermal BCG vaccines (author's transl)].

    Science.gov (United States)

    Fillastre, C; Guerin, N; Danusantoso, H; Sardadi, S

    1979-01-01

    Two BCG vaccines prepared from the same strain were studied clinically in Indonesia and in France. The concentration in culturable particles was comparable. Observed differences in the Mantoux results are discussed. The French results, based on use in a temperate climate by a specialized team, on well nourished children, appear better than the Indonesian findings. Further steps should be undertaken to improve results in Indonesia. PMID:539694

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

    Science.gov (United States)

    Braima, O; Rigney, A; Ryan, C A; Murphy, C

    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 (premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight. PMID:20669606

  3. A NOVEL BCG SENSOR-ARRAY FOR UNOBTRUSIVE CARDIAC MONITORING

    Directory of Open Access Journals (Sweden)

    Anna Böhm

    2013-12-01

    Full Text Available Unobtrusive heart rate monitoring is a popular research topic in biomedical engineering. The reason is that convential methods, e.g. the clinical gold standard electrocardiography, require conductive contact to the human body. Other methods such as ballistocardiography try to record these vital signs without electrodes that are attached to the body. So far, these systems cannot replace routine procedures. Most systems have some drawbacks that cannot be compensated, such as aging of the sensor materials or movement artifacts. In addition, the signal form differs greatly from an ECG, which is an electrical signal. The ballistocardiogram has a mechanical source, which makes it harder to evaluate. We have developed a new sensor array made of near-IR-LEDs to record BCGs. IR-sensors do not age in relevant time scales. Analog filtering was neccesary, because the signal amplitude was very small. The digitized data was then processed by various algorithms to extract beat-to-beat or breath-to-breath intervals. The redundancy of multiple BCG channels was used to provide a robust estimation of beat-to-beat intervals and heart rate. We installed the system beneath a mattress topper of a hospital bed, but any other bed would have been sufficient. The validation of this measurement system shows that it is well suited for BCG recordings. The use of multiple channels has proven to be superior to relying on a single BCG channel.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study

    DEFF Research Database (Denmark)

    Villumsen, Marie; Sørup, Signe; Jess, Tine;

    2009-01-01

    Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines...... cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.......31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas....

  6. 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.

  7. 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...

  8. Revaccination of Cattle with Bacille Calmette-Guérin Two Years after First Vaccination when Immunity Has Waned, Boosted Protection against Challenge with Mycobacterium bovis

    OpenAIRE

    Parlane, Natalie A.; Dairu Shu; Supatsak Subharat; D Neil Wedlock; Rehm, Bernd H. A.; Geoffrey W de Lisle; Buddle, Bryce M.

    2014-01-01

    In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB) and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 2½ years after vaccination and to determine the effect of revaccination after 2 years. Seventy-nine calves were divided into five groups (n = 15-17 calves/group) with four of the...

  9. 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

  10. 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......' 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....

  11. 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.

  12. 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.

  13. Biochemical characterization of the maltokinase from Mycobacterium bovis BCG

    Directory of Open Access Journals (Sweden)

    Lamosa Pedro

    2010-05-01

    Full Text Available Abstract Background Maltose-1-phosphate was detected in Mycobacterium bovis BCG extracts in the 1960's but a maltose-1-phosphate synthetase (maltokinase, Mak was only much later purified from Actinoplanes missouriensis, allowing the identification of the mak gene. Recently, this metabolite was proposed to be the intermediate in a pathway linking trehalose with the synthesis of glycogen in M. smegmatis. Although the M. tuberculosis H37Rv mak gene (Rv0127 was considered essential for growth, no mycobacterial Mak has, to date, been characterized. Results The sequence of the Mak from M. bovis BCG was identical to that from M. tuberculosis strains (99-100% amino acid identity. The enzyme was dependent on maltose and ATP, although GTP and UTP could be used to produce maltose-1-phosphate, which we identified by TLC and characterized by NMR. The Km for maltose was 2.52 ± 0.40 mM and 0.74 ± 0.12 mM for ATP; the Vmax was 21.05 ± 0.89 μmol/min.mg-1. Divalent cations were required for activity and Mg2+ was the best activator. The enzyme was a monomer in solution, had maximal activity at 60°C, between pH 7 and 9 (at 37°C and was unstable on ice and upon freeze/thawing. The addition of 50 mM NaCl markedly enhanced Mak stability. Conclusions The unknown role of maltokinases in mycobacterial metabolism and the lack of biochemical data led us to express the mak gene from M. bovis BCG for biochemical characterization. This is the first mycobacterial Mak to be characterized and its properties represent essential knowledge towards deeper understanding of mycobacterial physiology. Since Mak may be a potential drug target in M. tuberculosis, its high-level production and purification in bioactive form provide important tools for further functional and structural studies.

  14. Systemic BCG infection in a patient with pancytopaenia and fever 9 years after intravesical BCG administration for bladder cancer.

    Science.gov (United States)

    Westhovens, Ine M; Vanden Abeele, Marie-Elena; Messiaen, Peter E; van der Hilst, Jeroen Ch

    2016-01-01

    BCG is an attenuated live strain of Mycobacterium bovis that is used as an intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG instillation can lead to systemic diseases. We present a case of a 75-year-old man who was treated for recurrent localised transitional cell carcinoma (TCC) of the bladder with intravesical instillation of BCG in 2006. His medical history included Parkinson's disease. The patient reported worsening of Parkinson symptoms in the preceding month. In addition, he had progressive pancytopaenia and a bone marrow biopsy showed a granulomatous inflammatory infiltrate. Cultures from bone marrow aspiration grew M. bovis He was successfully treated with tuberculostatic drugs and made a full recovery. In addition, there was partial amelioration of the Parkinson symptoms. This case shows that physicians should be aware that BCG instillation for TCC can cause systemic disease even years after treatment. PMID:27170615

  15. Code system BCG for gamma-ray skyshine calculation

    International Nuclear Information System (INIS)

    A code system BCG has been developed for calculating conveniently and efficiently gamma-ray skyshine doses using the transport calculation codes ANISN and DOT and the point-kernel calculation codes G-33 and SPAN. To simplify the input forms to the system, the forms for these codes are unified, twelve geometric patterns are introduced to give material regions, and standard data are available as a library. To treat complex arrangements of source and shield, it is further possible to use successively the code such that the results from one code may be used as input data to the same or other code. (author)

  16. 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...... 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......-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrolment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus...

  17. Comparison of the fibronectin-binding ability and antitumor efficacy of various mycobacteria.

    Science.gov (United States)

    Hudson, M A; Ritchey, J K; Catalona, W J; Brown, E J; Ratliff, T L

    1990-07-01

    Although the mechanism by which Bacillus Calmette-Guerin (BCG) exerts an antitumor effect on superficial bladder tumors is not fully understood, recent evidence has implicated binding of BCG organisms to fibronectin (FN) as requisite for this antitumor efficacy. Various substrains of BCG and other mycobacteria were tested in vitro for their relative capacities to bind both matrix and soluble FN. A substrain of Mycobacterium kansasii, designated the "high-binding strain," was found to bind FN more readily (P less than 0.05) in in vitro studies, when compared to commercially available substrains of BCG (Tice, Connaught, and Armand Frappier). The binding by the three commercial strains of BCG to FN in vitro appeared to be equivalent. The high-binding strain was further demonstrated to attach more readily in vivo to the acutely injured murine bladder (P less than 0.005) than the Armand Frappier substrain. Finally, using the MB49 murine bladder tumor model, an enhanced antitumor effect (P less than 0.05) was noted in mice treated with intravesical high-binding strain, in comparison to the Armand Frappier substrain, during five weekly treatments. It appears not only that the commercial substrains of BCG bind FN in an equivalent manner but also that the relative binding capacities of the substrains correlate directly with antitumor activity. A substrain of M. kansasii appears to have been identified which may prove more clinically effective than the currently available strains of BCG.

  18. 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.

  19. 卫生部免疫规划专家咨询委员会的作用

    Institute of Scientific and Technical Information of China (English)

    郑景山; 王华庆; 周玉清; 殷大鹏; 梁晓峰

    2010-01-01

    @@ 1 背景我国从1978年开始实施计划免疫,按照统一的免疫程序为适龄儿童提供卡介苗(Bacillus Calmette Guerin,BCG)、口服脊髓灰质炎(脊灰)减毒活疫苗(Oral Poliomyelitis Attenuated Live Vaccine,OPV)、麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)和百日咳-白喉-破伤风联合疫苗(Diphtheria,Tetanus,Pertussis Combined Vaccine,DPT)接种,预防结核、脊灰、麻疹、百日咳、白喉、破伤风6种常见传染病.

  20. 一起预防接种实施差错事故引发的思考

    Institute of Scientific and Technical Information of China (English)

    耿晓冬

    2011-01-01

    某患儿,男,2009年4月19日出生,无疫苗接种禁忌证和过敏史,既往已经接种了卡介苗(Bacillus Calmette Guerin,BCG)1剂、乙型病毒性肝炎(乙肝)疫苗(Hepatitis B Vaccine,HepB)2剂、百日咳-白喉-破伤风联合疫苗( Diphtheria,Tetanus,Pertussis Combined Vaccine,DPT)3剂、脊髓灰质炎疫苗(Oral Poliomyelitis Attenuated Live Vaccine,OPV)3剂,家长自述过往接种疫苗未发现异常反应,家族无患病史.

  1. The role of vitamin D in malaria.

    Science.gov (United States)

    Lương, Khanh Vinh Quốc; Nguyễn, Lan Thi Hoàng

    2015-01-15

    An abnormal calcium-parathyroid hormone (PTH)-vitamin D axis has been reported in patients with malaria infection. A role for vitamin D in malaria has been suggested by many studies. Genetic studies have identified numerous factors that link vitamin D to malaria, including human leukocyte antigen genes, toll-like receptors, heme oxygenase-1, angiopoietin-2, cytotoxic T lymphocyte antigen-4, nucleotide-binding oligomerization domain-like receptors, and Bcl-2. Vitamin D has also been implicated in malaria via its effects on the Bacillus Calmette-Guerin (BCG) vaccine, matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, reactive oxidative species, and nitric oxide synthase. Vitamin D may be important in malaria; therefore, additional research on its role in malaria is needed.

  2. 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...... 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...

  3. 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...

  4. 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.

  5. A Point Mutation in the mma3 Gene Is Responsible for Impaired Methoxymycolic Acid Production in Mycobacterium bovis BCG Strains Obtained after 1927

    OpenAIRE

    Behr, Marcel A.; Schroeder, Benjamin G.; Brinkman, Jacquelyn N.; Slayden, Richard A.; Barry, Clifton E.

    2000-01-01

    BCG vaccines are substrains of Mycobacterium bovis derived by attenuation in vitro. After the original attenuation (1908 to 1921), BCG strains were maintained by serial propagation in different BCG laboratories (1921 to 1961). As a result, various BCG substrains developed which are now known to differ in a number of genetic and phenotypic properties. However, to date, none of these differences has permitted a direct phenotype-genotype link. Since BCG strains differ in their abilities to synth...

  6. "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.

  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. Recombinant Mycobacterium bovis BCG secreting functional interleukin-2 enhances gamma interferon production by splenocytes.

    OpenAIRE

    O'Donnell, M A; Aldovini, A; Duda, R B; Yang, H; Szilvasi, A; Young, R A; DeWolf, W C

    1994-01-01

    Mycobacterium bovis BCG was genetically engineered to express and secrete mouse interleukin-2 (IL-2) and rat IL-2. Genes encoding IL-2 were inserted into an Escherichia coli-BCG shuttle plasmid under the control of the BCG HSP60 promoter. To facilitate study of proteins produced in this system, the IL-2 gene product was expressed (i) alone, (ii) with the mycobacterial alpha-antigen secretion signal sequence at the amino terminus, (iii) with an influenza virus hemagglutinin epitope tag at the ...

  9. 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.

  10. 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...

  11. 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....

  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. 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.

  14. The use of directed evolution to create a stable and immunogenic recombinant BCG expressing a modified HIV-1 Gag antigen.

    Directory of Open Access Journals (Sweden)

    Rosamund Chapman

    Full Text Available Numerous features make Mycobacterium bovis BCG an attractive vaccine vector for HIV. It has a good safety profile, it elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable. Despite these advantages it is often difficult to express viral antigens in BCG, which results in genetic instability and low immunogenicity. The aim of this study was to generate stable recombinant BCG (rBCG that express high levels of HIV antigens, by modification of the HIV genes. A directed evolution process was applied to recombinant mycobacteria that expressed HIV-1 Gag fused to the green fluorescent protein (GFP. Higher growth rates and increased GFP expression were selected for. Through this process a modified Gag antigen was selected. Recombinant BCG that expressed the modified Gag (BCG[pWB106] and BCG[pWB206] were more stable, produced higher levels of antigen and grew faster than those that expressed the unmodified Gag (BCG[pWB105]. The recombinant BCG that expressed the modified HIV-1 Gag induced 2 to 3 fold higher levels of Gag-specific CD4 T cells than those expressing the unmodified Gag (BCG[pWB105]. Mice primed with 10(7 CFU BCG[pWB206] and then boosted with MVA-Gag developed Gag-specific CD8 T cells with a frequency of 1343±17 SFU/10(6 splenocytes, 16 fold greater than the response induced with MVA-Gag alone. Levels of Gag-specific CD4 T cells were approximately 5 fold higher in mice primed with BCG[pWB206] and boosted with MVA-Gag than in those receiving the MVA-Gag boost alone. In addition mice vaccinated with BCG[pWB206] were protected from a surrogate vaccinia virus challenge.

  15. The use of directed evolution to create a stable and immunogenic recombinant BCG expressing a modified HIV-1 Gag antigen.

    Science.gov (United States)

    Chapman, Rosamund; Bourn, William R; Shephard, Enid; Stutz, Helen; Douglass, Nicola; Mgwebi, Thandi; Meyers, Ann; Chin'ombe, Nyasha; Williamson, Anna-Lise

    2014-01-01

    Numerous features make Mycobacterium bovis BCG an attractive vaccine vector for HIV. It has a good safety profile, it elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable. Despite these advantages it is often difficult to express viral antigens in BCG, which results in genetic instability and low immunogenicity. The aim of this study was to generate stable recombinant BCG (rBCG) that express high levels of HIV antigens, by modification of the HIV genes. A directed evolution process was applied to recombinant mycobacteria that expressed HIV-1 Gag fused to the green fluorescent protein (GFP). Higher growth rates and increased GFP expression were selected for. Through this process a modified Gag antigen was selected. Recombinant BCG that expressed the modified Gag (BCG[pWB106] and BCG[pWB206]) were more stable, produced higher levels of antigen and grew faster than those that expressed the unmodified Gag (BCG[pWB105]). The recombinant BCG that expressed the modified HIV-1 Gag induced 2 to 3 fold higher levels of Gag-specific CD4 T cells than those expressing the unmodified Gag (BCG[pWB105]). Mice primed with 10(7) CFU BCG[pWB206] and then boosted with MVA-Gag developed Gag-specific CD8 T cells with a frequency of 1343±17 SFU/10(6) splenocytes, 16 fold greater than the response induced with MVA-Gag alone. Levels of Gag-specific CD4 T cells were approximately 5 fold higher in mice primed with BCG[pWB206] and boosted with MVA-Gag than in those receiving the MVA-Gag boost alone. In addition mice vaccinated with BCG[pWB206] were protected from a surrogate vaccinia virus challenge. PMID:25061753

  16. 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.

  17. Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination

    OpenAIRE

    Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

    2015-01-01

    Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history ...

  18. Genetic control of antibody responses induced by recombinant Mycobacterium bovis BCG expressing a foreign antigen.

    OpenAIRE

    Lagranderie, M; Lo-Man, R; Dériaud, E; Gicquel, B; Gheorghiu, M; Leclerc, C

    1997-01-01

    Recombinant Mycobacterium bovis BCG expressing foreign antigens represents a promising candidate for the development of future vaccines and was shown in several experimental models to induce protective immunity against bacterial or parasitic infections. Innate resistance to BCG infection is under genetic control and could modify the immune responses induced against an antigen delivered by such engineered microorganisms. To investigate this question, we analyzed the immune responses of various...

  19. Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

    OpenAIRE

    Sarman Singh; Manoj Kumar; Pragati Singh

    2015-01-01

    BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive ...

  20. Mantoux test results and BCG vaccination status in TB-exposed children

    OpenAIRE

    Fadilah Harahap; Ridwan M. Daulay; Muhammad Ali; Wisman Dalimunthe; Rini Savitri Daulay

    2016-01-01

    Background Tuberculosis (TB) infection is highly prevalent in Indonesia. The source of transmission of TB to a child is usually via an adult with sputum smear-positive pulmonary tuberculosis. The Mantoux test is a diagnostic tool for tuberculosis infection. The BCG vaccine has been used for the prevention of TB, but its efficacy is still debated. Objective To assess for an association between Mantoux test results and BCG vaccination in children who had contact with adult pulmonary tuberculosi...

  1. [Sepsis and multiple organ failure after BCG-instillation for bladder cancer].

    Science.gov (United States)

    Elmer, A; Bermes, U; Drath, L; Büscher, E; Viertel, A

    2004-08-01

    Local Bacillus Calmette-Guérin (BCG) immunotherapy is an effective and widely used treatment for superficial bladder carcinoma. Local side effects are frequent, whereas systemic side effects are rare, but more serious. Systemic BCG infection as a life-threatening complication of intravesical BCG instillation should be suspected in any patient who presents with persistent fever after BCG instillation for bladder cancer. A 62-year-old patient had been treated with 6 intravesical BCG instillations for recurrent, multifocal bladder carcinoma. 4 weeks after the last instillation, he presented with fever, malaise and scleral icterus. Laboratory tests revealed abnormal liver function tests, panzytopenia and signs of coagulation disorder. Bone marrow biopsy and liver biopsy showed noncaseating granulomas. Systemic BCG infection was suspected and antituberculous therapy combined with steroids was started. The patient developed severe sepsis and suffered from multiple organ failure. Despite partial improvement, the course was complicated by intracranial sinus thrombosis, and the patient died two month after admission. PMID:15138643

  2. 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.

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

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    M. J. Pereira Filho

    1955-12-01

    Full Text Available The reversals of Mitsuda's reactions induced by BCG have been objected to based on the possiblem interference of other determination causes of the phenomenon: tuberculous primo-infections, communicants of unsuspected leprosy, revearsals due to other causes, such as anti-diphteric and anti-tetanic vaccination, etc. In order to study the problem, we have used Rhesus monkeys (Macaca mulatta, which were reared in isolation, in an attempt to avoid the referred to interferences. Prior to the experiments, all animals were tested and found negative to radiograph, tuberculin and lepromin tests and were then submitted to the application of BCG vaccine (from 1 to 3 days old, in different doses and by different via. At different times, after the application of BCG, they were again submitted to the radiographic, tuberculin and lepromin tests. In the tables I to IV the experiences were summarised. From the experiments, the following conclusions were reached: 1 - From 12 Rhesus that received BCG 11 showed reversals of the Mitsuda reaction (91.7%. 2 - These reverseals took place both in tests effected shortly after BCG (from 6 days to 2 months, and tests effected much later (from 7 to 12 months after BCG. 3 - Some differences were found in the results, according to the dosis and the application via of the BCG. a - The testicular and peritonela via (0,02g were the only that determined strong positive Mitsuda's reactions (+++. b - By oral via, animals that received high dosis (0.6g and 1.2 g, there resulted uniform and regular reversals, even though of low intensity (+; but from those who got small doses (0.2 g. one showed no reversals in all tests, and the other presented reversals in the 2nd and 3rd tests only, also with low positivity (+. 4 In the 2nd and 3rd Mitsuda's reactions in the same animals, positivity was always precocious (generally within 48 hours, one getting the impression that there occurs a sensibilization of the animal body by the antigen with

  4. 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

    reactors (>1mm) after BCG vaccination was 25% and the rate of scarring was 89%. One BCG strain was associated with fewer PPD reactors (OR=0.54 (0.31-0.91)) and BCG scars (OR=0.13 (0.05-0.37)) and larger post-vaccination wheals produced more PPD reactions (OR 1.21 (95% CI 1.02-1.43)) and BCG scars (OR 1.......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...

  5. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial

    OpenAIRE

    Benn, Christine Stabell; Fisker, Ane Bærent; Napirna, Bitiguida Mutna; Roth, Adam; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Ravn, Henrik; Yazdanbakhsh, Maria; Rodrigues, Amabelia; Whittle, Hilton; Aaby, Peter

    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...

  6. Emerging intravesical therapies for management of nonmuscle invasive bladder cancer

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    Jeffrey J Tomaszewski

    2010-05-01

    Full Text Available Jeffrey J Tomaszewski, Marc C SmaldoneDepartment of Urology, University of Pittsburgh School of Medicine, Pennsylvania, USAAbstract: Transitional cell carcinoma (TCC is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer (NMIBC. Intravesical bacillus Calmette-Guerin (BCG is the most effective agent for preventing disease recurrence, and the only therapy able to inhibit disease progression. However, recurrence rates as high as 30% and significant local and systemic toxicity have led to increased interest in alternative intravesical therapies. In patients refractory or intolerant to BCG, BCG-interferon α2b, gemcitabine, and anthracyclines (doxorubicin, epirubicin, valrubicin have demonstrated durable clinical responses. Phase I trials investigating alternative cytotoxic agents, such as apaziquone, taxanes (docetaxel, paclitaxel, and suramin are reporting promising data. Novel immunomodulating agents have demonstrated promise as efficacious alternatives in patients refractory to BCG. Optimization of existing chemotherapeutic regimens using hyperthermia, photodynamic therapy, magnetically-targeted carriers, and liposomes remains an area of active investigation. Despite enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and selected patients with naïve T1 tumors and aggressive features. This report provides a comprehensive review of contemporary intravesical therapy for NMIBC and refractory NMIBC, with an emphasis on emerging agents and novel treatment modalities.Keywords: transitional cell carcinoma, nonmuscle, invasive, intravesical therapy, BCG

  7. [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.

  8. Parenteral adenoviral boost enhances BCG induced protection, but not long term survival in a murine model of bovine TB.

    Science.gov (United States)

    Kaveh, Daryan A; Garcia-Pelayo, M Carmen; Webb, Paul R; Wooff, Esen E; Bachy, Véronique S; Hogarth, Philip J

    2016-07-25

    Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes. This induces significant improvement in pulmonary protection against Mycobacterium bovis over that provided by BCG when assessed in a standard 4week challenge model. However, in a stringent, year-long survival study, BCG/Ad-TB10.4 did not improve outcome over BCG, which we suggest may be due to the lack of additional memory cells (IL-2(+)) induced by boosting. These data indicate BCG-prime/parenteral-Ad-TB10.4-boost to be a promising candidate, but also highlight the need for further understanding of the mechanisms of T cell priming and associated memory using Ad delivery systems. That we were able to generate significant improvement in pulmonary protection above BCG with parenteral, rather than mucosal administration of boost vaccine is critical; suggesting that the generation of effective mucosal immunity is possible, without the risks and challenges of mucosal administration, but that further work to specifically enhance sustained protective immunity is required. PMID:27317453

  9. [Rifampicin-resistant Mycobacterium bovis BCG strain isolated from an infant with NEMO mutation].

    Science.gov (United States)

    Çavuşoğlu, Cengiz; Edeer Karaca, Neslihan; Azarsız, Elif; Ulusoy, Ezgi; Kütükçüler, Necil

    2015-04-01

    It is well known that disseminated Mycobacterium bovis BCG infection is developed after BCG vaccination in infants with congenital cellular immune deficiencies such as mutations in genes along the interleukin (IL)-12/interferon (IFN)-γ pathway and mutations in nuclear factor-kB essential modulator (NEMO). In this report, a rifampicin-resistant M.bovis BCG strain isolated from an infant with NEMO defect was presented. An 8-month-old male infant with NEMO defect admitted to the pediatric outpatient clinic of our hospital with fever, generalized lymphadenopathy and hepatosplenomegaly. Microscopic examination of the smears prepared from lymph node and liver biopsy specimens revealed abundant amount (3+) of acid-fast bacilli (AFB). Rifampicin-susceptible Mycobacterium tuberculosis complex (MTC) was detected by real-time PCR (GeneXpert MTB/RIF; Cepheid, USA) in the samples. The growth of mycobacteria was determined on the 20th day of culture performed in MGIT960 system (Becton Dickinson, USA). The isolate was identified as M.bovis BCG by GenoType MTBC kit (Hain Lifescience, Germany) and defined as M.bovis BCG [SIT 482 (BOV_1)] by spoligotyping. In the primary anti-tuberculosis drug susceptibility test performed by MGIT960 system, the isolate was found susceptible to rifampicin (RIF), isoniazid (INH), streptomycin (STM) and ethambutol (EMB). Then anti-tuberculosis treatment was started to the patient. However, the patient at the age of 2 years, re-admitted to the hospital with the complaint of hepatosplenomegaly. Smear of spontaneously draining abscess material obtained from subcutaneous nodules revealed intensive AFB positivity (3+) once again. In the present instance RIF-resistant MTC was detected with GeneXpert system in the specimen. The growth of mycobacteria was determined on the 13th day of culture and isolate was identified as M.bovis BCG. The present isolate was found susceptible to INH, STM and EMB but resistant to RIF. A mutation in the rpoB gene (codon 531, S

  10. Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

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    Sarman Singh

    2015-01-01

    Full Text Available BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine.

  11. Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

    Science.gov (United States)

    Singh, Sarman; Kumar, Manoj; Singh, Pragati

    2015-01-01

    BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine. PMID:25694828

  12. Effect of the injection of an extract of Ascaris suum on macrophage activation during the early phase of Mycobacterium bovis BCG infection in C57Bl/6 mice

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    Ferreira A.P.

    1999-01-01

    Full Text Available Injection of an Ascaris suum extract (Asc affects both the humoral and cellular immune responses to unrelated antigens when it is co-administered with these antigens. In the present study we evaluated the effect of Asc on macrophage activation in the early phase of Mycobacterium bovis BCG (Pasteur strain TMCC 1173 infection in C57Bl/6 mice. C57Bl/6 mice were injected intraperitoneally (ip with 0.1 mg BCG (BCG group or BCG plus 1 mg Asc (BCG + Asc group. The peritoneal exudates were obtained at 2, 7 and 14 days after infection. The numbers of IFN-g-secreting cells were assessed by the ELISPOT assay. Nitric oxide (NO production was measured by the Griess method and by the evaluation of NADPH diaphorase activity in the peritoneal exudates. The administration of Asc extract increased NADPH diaphorase activity (2 days: control = 0, BCG = 7%, BCG + Asc = 13%, and Asc = 4%; 7 days: control = 4, BCG = 13%, BCG + Asc = 21%, and Asc = 4.5% and TNF-a levels (mean ± SD; 2 days: control = 0, BCG = 169 ± 13, BCG + Asc = 202 ± 37, and Asc = 0; 7 days: control = 0, BCG = 545 ± 15.5, BCG + Asc = 2206 ± 160.6, and Asc = 126 ± 26; 14 days: control = 10 ± 1.45, BCG = 9 ± 1.15, BCG + Asc = 126 ± 18, and Asc = 880 ± 47.67 pg/ml in the early phase of BCG infection. Low levels of NO production were detected at 2 and 7 days after BCG infection, increasing at 14 days (mean ± SD; 2 days: control = 0, BCG = 3.7 ± 1.59, BCG + Asc = 0.82 ± 0.005, Asc = 0.48 ± 0.33; 7 days: control = 0, BCG = 2.78 ± 1.54, BCG + Asc = 3.07 ± 1.05, Asc = 0; 14 days: control = 0, BCG = 9.05 ± 0.53, BCG + Asc = 9.61 ± 0.81, Asc = 10.5 ± 0.2 (2 x 106 cells/ml. Furthermore, we also observed that Asc co-injection induced a decrease of BCG-colony-forming units (CFU in the spleens of BCG-infected mice during the first week of infection (mean ± SD; 2 days: BCG = 1.13 ± 0.07 and BCG + Asc = 0.798 ± 0.305; 7 days: BCG = 1.375 ± 0.194 and BCG + Asc = 0.548 ± 0.0226; 14 days: BCG

  13. BCG Vaccination as a Prevention Strategy, Threats and Benefits

    Directory of Open Access Journals (Sweden)

    Shirvani

    2016-04-01

    Full Text Available Context Tuberculosis is still one of the deadliest communicable diseases. Objectives Nine million people worldwide developed TB in 2013, and 1.5 million people died from it, 360000 of which were HIV positive. Although the disease is controllable by means of diagnostic and treatment measures, the death toll from the disease is still high, and efforts to combat it must be accelerated. Data Sources Data compiled from 202 countries in the Global Tuberculosis Report 2014 showed that TB is present in all regions of the world. Study Selection Higher numbers of tuberculosis cases were diagnosed in 2013 in comparison with previous reports, indicating that diagnoses and reports of new cases may be improved by stringent data collection. Data Extraction A special note to the 2014 report highlighted the progress of drug resistant TB during the last two decades. Results Worldwide, a proportion of new cases with multidrug-resistant TB (MDR-TB were reported at 3.5% in 2013 without a significant change compared with recent years. Interestingly, higher levels of resistance and poor treatment outcomes are of major concern in some parts of the world. Due to this concern, special attention is focused on prevention rather than treatment. On the other hand, the effectiveness of an existing vaccine (BCG is increasingly questionable. Conclusions It has the potential to cause disseminated infection, and an increasing number of immunocompromised patients prone to disease and the suboptimal preventive potency of this vaccine suggest the need for a global attempt to review its benefits and disadvantages.

  14. 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

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    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.

  15. 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;

    of illness and atopic diseases in their personal network and family to evaluate risk for their child to develop atopic diseases or get hospitalised. This lay epidemiologi forms the basis for their decision. Davison C, Frankel S, Davey Smith G. Inheriting heart trouble: the relevance of common-sense ideas......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...

  16. 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.

  17. Non-specific effect of BCG vaccination at birth on early childhood infections. A randomized, clinical multicenter trial

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Birk, Nina M; Nissen, Thomas N;

    2016-01-01

    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......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...... 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...

  18. WHO Informal Consultation on standardization and evaluation of BCG vaccines Geneva, Switzerland 22-23 September 2009.

    Science.gov (United States)

    Ho, Mei M; Southern, James; Kang, Hye-Na; Knezevic, Ivana

    2010-10-01

    The current World Health Organization Requirements for BCG vaccine are in need of revision to address the diversity of sub-strains used for production, potential improvements of quality control assays for lot release, and the establishment of sub-strain specific Reference Reagents. A consultation meeting was organized to discuss issues regarding the standardization and evaluation of BCG vaccines in the forum of regulators, BCG vaccine manufacturers, developers of selected new live tuberculosis (TB) vaccines and researchers. The development of new recombinant BCG and live attenuated TB vaccines and the characterisation of different BCG sub-strains using state-of-the-art technologies were also reviewed. The objective of the meeting was to revise and update the current recommendations focused on the scope, terminology, manufacturing issues, and the incorporation of new reference reagents and new quality control tests. PMID:20692219

  19. Size characterization of Mycobacterium bovis BCG (Bacillus Calmette Guérin) vaccine, Tice substrain.

    Science.gov (United States)

    Zhang, A; Groves, M J

    1988-09-01

    Reconstituted, lyophilized, attenuated Mycobacterium bovis, Bacillus Calmette Guérin (BCG) vaccine, Tice substrain, was characterized using a Coulter Multisizer and a HIAC/Royco counter. The primary organism has an equivalent spherical diameter approximating 1 micron but the BCG cell suspension is heavily aggregated. The cumulative size distribution of the suspension fits a log-probit plot and this information can be used to determine the total number of particles per ampoule. The instrumental count may be related to the viable count. The state of dispersion was unaffected by mild shear (syringe aspiration or ultrasound) and only slightly affected by the addition of cetylpyridinium chloride or sodium tauroglycolate. PMID:3073388

  20. 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.

  1. The Ag85B protein of the BCG vaccine facilitates macrophage uptake but is dispensable for protection against aerosol Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Prendergast, Kelly A; Counoupas, Claudio; Leotta, Lisa; Eto, Carolina; Bitter, Wilbert; Winter, Nathalie; Triccas, James A

    2016-05-17

    Defining the function and protective capacity of mycobacterial antigens is crucial for progression of tuberculosis (TB) vaccine candidates to clinical trials. The Ag85B protein is expressed by all pathogenic mycobacteria and is a component of multiple TB vaccines under evaluation in humans. In this report we examined the role of the BCG Ag85B protein in host cell interaction and vaccine-induced protection against virulent Mycobacterium tuberculosis infection. Ag85B was required for macrophage infection in vitro, as BCG deficient in Ag85B expression (BCG:(Δ85B)) was less able to infect RAW 264.7 macrophages compared to parental BCG, while an Ag85B-overexpressing BCG strain (BCG:(oex85B)) demonstrated improved uptake. A similar pattern was observed in vivo after intradermal delivery to mice, with significantly less BCG:(Δ85B) present in CD64(hi)CD11b(hi) macrophages compared to BCG or BCG:(oex85B). After vaccination of mice with BCG:(Δ85B) or parental BCG and subsequent aerosol M. tuberculosis challenge, similar numbers of activated CD4(+) and CD8(+) T cells were detected in the lungs of infected mice for both groups, suggesting the reduced macrophage uptake observed by BCG:(Δ85B) did not alter host immunity. Further, vaccination with both BCG:(Δ85B) and parental BCG resulted in a comparable reduction in pulmonary M. tuberculosis load. These data reveal an unappreciated role for Ag85B in the interaction of mycobacteria with host cells and indicates that single protective antigens are dispensable for protective immunity induced by BCG. PMID:27060378

  2. BCG-MSG Medium on Identification of Common Filamentous Fungi%BCG-MSG培养基鉴定几种常见的丝状真菌

    Institute of Scientific and Technical Information of China (English)

    鲁长明; 席丽艳; 谢穗生; 张军民

    2004-01-01

    目的寻找一种鉴定丝状真菌的新培养基.方法选择常见的6种皮肤癣菌和申克孢子丝菌,采用自行配制的溴甲酚绿奶粉葡萄糖琼脂培养基(BCG-MSG)培养,并与马玲薯葡萄糖琼脂和沙堡弱琼脂两种培养基的菌落形态进行比较,在5天、7天、14天记录色素的形成情况,总观察时间为14天.结果红色毛癣菌在BCG-MSG上产色快,其他皮肤癣菌色素变化不大,只是色素比较鲜艳.结论 BCG-MSG培养基具有产色效果好而快,直观感好和配制简单等特点,值得推广应用.

  3. The BCGΔBCG1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo.

    Science.gov (United States)

    Pedroza-Roldán, César; Guapillo, Carolina; Barrios-Payán, Jorge; Mata-Espinosa, Dulce; Aceves-Sánchez, Michel de Jesús; Marquina-Castillo, Brenda; Hernández-Pando, Rogelio; Flores-Valdez, Mario Alberto

    2016-09-14

    Mycobacterium tuberculosis (Mtb) has been a threat to humans since ancient times, and it is the main causative agent of tuberculosis (TB). Until today, the only licensed vaccine against Mtb is the live attenuated M. bovis Bacillus Calmette-Guérin (BCG), which has variable levels of protection against the pulmonary form of infection. The quest for a new vaccine is a priority given the rise of multidrug-resistant Mtb around the world, as well as the tremendous burden imposed by latent TB. The objective of this study was to evaluate the immunogenicity and capacity of protection of a modified BCG strain (BCGΔBCG1419c) lacking the c-di-GMP phosphodiesterase gene BCG1419c, in diverse mice models. In a previous report, we have shown that BCGΔBCG1419c was capable of increasing biofilm production and after intravenous infection of immunocompetent mice; this strain persisted longer in lungs than parental BCG Pasteur. This led us to hypothesize that BCGΔBCG1419c might therefore possess some advantage as vaccine candidate. Our results in this report indicate that compared to conventional BCG, vaccination with BCGΔBCG1419c induced a better activation of specific T-lymphocytes population, was equally effective in preventing weight loss despite being used at lower dose, reduced tissue damage (pneumonic scores), increased local IFNγ(+) T cells, and diminished bacterial burden in lungs of BALB/c mice infected intratracheally with high dose Mtb H37Rv to induce progressive TB. Moreover, vaccination with BCGΔBCG1419c improved resistance to reactivation after immunosuppression induced by corticosterone in a murine model of chronic infection similar to latent TB. Furthermore, despite showing increased persistence in immunocompetent mice, BCGΔBCG1419c was as attenuated as parental BCG in nude mice. To our knowledge, this is the first demonstration that a modified BCG vaccine candidate with increased pellicle/biofilm production has the capacity to protect against Mtb challenge in

  4. Dose of Incorporated Immunodominant Antigen in Recombinant BCG Impacts Modestly on Th1 Immune Response and Protective Efficiency against Mycobacterium tuberculosis in Mice

    Directory of Open Access Journals (Sweden)

    Hui Ma

    2014-01-01

    Full Text Available One approach for improving BCG efficacy is to utilize BCG as vehicle to develop recombinant BCG (rBCG strains overexpressing Mycobacterium tuberculosis (M. tb antigens. Also expression level of a candidate antigen should impact the final T cell responses conferred by rBCG. In this study, based on our previously constructed differential expression system, we developed two rBCG strains overexpressing M. tb chimeric antigen Ag856A2 (coding a recombinant ag85a with 2 copies of esat-6 inserted at Acc I site of ag85a at differential levels under the control of the subtly modified furA promoters. These two rBCG strains were used to vaccinate C57BL/6 mice and exploit dose of incorporated antigen in rBCG to optimize immune response and protective efficiency against M. tb challenge in mouse model. The results showed that rBCG strains overexpressing Ag856A2 at differential levels induced different antigen-specific IFN-γ production and comparable number of M. tb-specific CD4 T cells expressing IL-2. M. tb challenge experiment showed that rBCG strains afforded enhanced but comparable immune protection characterized by reduced bacillary load, lung pathology, and inflammation. These results suggested that the dose of antigens incorporated in rBCG can impact T cell immune responses but imposed no significantly differential protective efficacies.

  5. 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

    2016-01-01

    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. PMID:27173443

  6. 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. PMID:17888740

  7. Multifocal sclerotic BCG spondylitis in a 13-year-old girl

    International Nuclear Information System (INIS)

    A case is reported of multifocal BCG osteomyelitis in a 13-year-old girl. The lesions in the skull, ribs and in several vertebrae were mainly sclerotic and healed with antituberculotic therapy. The case is unusual because of the late onset, sclerotic changes, and involvement of the spine. (orig.)

  8. Targeted BCG Vaccination Against Severe Tuberculosis in Low-prevalence Settings Epidemiologic and Economic Assessment

    NARCIS (Netherlands)

    H. Korthals Altes; F. Dijkstra; A. Lugnèr; F. Cobelens; J. Wallinga

    2009-01-01

    Background: BCG vaccine protects against the severe forms of tuberculosis (TB) in children. Several low-prevalence countries are reviewing their policy, usually shifting from universal vaccination to vaccination of infants in high-risk groups only. We combined an epidemiologic analysis with a cost-e

  9. 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.

  10. 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

  11. Evaluation of the Immunogenicity of Mycobacterium bovis BCG Delivered by Aerosol to the Lungs of Macaques.

    Science.gov (United States)

    White, A D; Sarfas, C; West, K; Sibley, L S; Wareham, A S; Clark, S; Dennis, M J; Williams, A; Marsh, P D; Sharpe, S A

    2015-09-01

    Nine million cases of tuberculosis (TB) were reported in 2013, with a further 1.5 million deaths attributed to the disease. When delivered as an intradermal (i.d.) injection, the Mycobacterium bovis BCG vaccine provides limited protection, whereas aerosol delivery has been shown to enhance efficacy in experimental models. In this study, we used the rhesus macaque model to characterize the mucosal and systemic immune response induced by aerosol-delivered BCG vaccine. Aerosol delivery of BCG induced both Th1 and Th17 cytokine responses. Polyfunctional CD4 T cells were detected in bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMCs) 8 weeks following vaccination in a dose-dependent manner. A similar trend was seen in peripheral gamma interferon (IFN-γ) spot-forming units measured by enzyme-linked immunosorbent spot (ELISpot) assay and serum anti-purified protein derivative (PPD) IgG levels. CD8 T cells predominantly expressed cytokines individually, with pronounced tumor necrosis factor alpha (TNF-α) production by BAL fluid cells. T-cell memory phenotype analysis revealed that CD4 and CD8 populations isolated from BAL fluid samples were polarized toward an effector memory phenotype, whereas the frequencies of peripheral central memory T cells increased significantly and remained elevated following aerosol vaccination. Expression patterns of the α4β1 integrin lung homing markers remained consistently high on CD4 and CD8 T cells isolated from BAL fluid and varied on peripheral T cells. This characterization of aerosol BCG vaccination highlights features of the resulting mycobacterium-specific immune response that may contribute to the enhanced protection previously reported in aerosol BCG vaccination studies and will inform future studies involving vaccines delivered to the mucosal surfaces of the lung. PMID:26108288

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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 Guinea......, particularly of the cytokines IL-1β, IL-6, TNF-α, and IFN-γ. CONCLUSION:  Four weeks after immunization, BCG-vaccinated infants have a significantly increased production of cytokines upon heterologous challenge, particularly T helper cell type 1 polarizing and typically monocyte-derived pro...

  14. Mitogen-activated protein kinases and NFκB are involved in SP-A-enhanced responses of macrophages to mycobacteria

    Directory of Open Access Journals (Sweden)

    Vigerust David J

    2009-07-01

    Full Text Available Abstract Background Surfactant protein A (SP-A is a C-type lectin involved in surfactant homeostasis as well as host defense in the lung. We have recently demonstrated that SP-A enhances the killing of bacillus Calmette-Guerin (BCG by rat macrophages through a nitric oxide-dependent pathway. In the current study we have investigated the role of tyrosine kinases and the downstream mitogen-activated protein kinase (MAPK family, and the transcription factor NFκB in mediating the enhanced signaling in response to BCG in the presence of SP-A. Methods Human SP-A was prepared from alveolar proteinosis fluid, and primary macrophages were obtained by maturation of cells from whole rat bone marrow. BCG-SP-A complexes were routinely prepared by incubation of a ratio of 20 μg of SP-A to 5 × 105 BCG for 30 min at 37°C. Cells were incubated with PBS, SP-A, BCG, or SP-A-BCG complexes for the times indicated. BCG killing was assessed using a 3H-uracil incorporation assay. Phosphorylated protein levels, enzyme assays, and secreted mediator assays were conducted using standard immunoblot and biochemical methods as outlined. Results Involvement of tyrosine kinases was demonstrated by herbimycin A-mediated inhibition of the SP-A-enhanced nitric oxide production and BCG killing. Following infection of macrophages with BCG, the MAPK family members ERK1 and ERK2 were activated as evidence by increased tyrosine phosphorylation and enzymatic activity, and this activation was enhanced when the BCG were opsonized with SP-A. An inhibitor of upstream kinases required for ERK activation inhibited BCG- and SP-A-BCG-enhanced production of nitric oxide by approximately 35%. Macrophages isolated from transgenic mice expressing a NFκB-responsive luciferase gene showed increased luciferase activity following infection with BCG, and this activity was enhanced two-fold in the presence of SP-A. Finally, lactacystin, an inhibitor of IκB degradation, reduced BCG- and SP-A-BCG

  15. A polymerase chain reaction and enzyme linked immunosorbent assay based approach for diagnosis and differentiation between vaccinated and infected cattle with Mycobacterium bovis

    Directory of Open Access Journals (Sweden)

    Mohamed Sabry

    2014-01-01

    Full Text Available Background: In most African and Arabic countries tuberculosis (TB causes great economic losses in bovine species and constitutes serious zoonotic problem. As the traditional diagnostic method delay the research because of low sensitivity and specificity, a rapid method of diagnosis is of outmost importance. Aim: The study was designed to evaluate the two rapid diagnostic methods of TB in cattle, further to differentiate between infected and bacillus Calmette-Guerin (BCG vaccinated animals. Materials and Methods: Intradermal tuberculin test was applied to 300 cattle. Of these cattle, 15 cattle were vaccinated from cattle negative to tuberculin test with BCG. Blood samples were taken for lymphocyte separation to apply polymerase chain reaction (PCR upon and for serum preparation for the enzyme-linked immunosorbent assay (ELISA application, this blood collected from 65 cattle classified into three groups, viz. positive tuberculin test (35 animals, negative tuberculin test (15 animals, and vaccinated cow with BCG (15 animals. From blood samples lymphocytes were separated and the isolated lymphocytes were subjected to PCR and serum for ELISA application. Blood samples, specimens from lymph nodes and specific tissues were taken for PCR and for cultivation and isolation of Mycobacterium bovis. Results and Conclusions: The results of this study revealed that PCR can be used as rapid efficient and accurate diagnostic test in detection of ruminant TB. Moreover, cattle′s ELISA reading showed higher sensitivity in positive tuberculin animals. However, the differentiations between vaccinated and infected animals not clear by using a single antigen only.

  16. 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.

  17. Theoretical and methodological aspects of BCG vaccine from the discovery of Calmette and Guérin to molecular biology. A review.

    Science.gov (United States)

    Lugosi, L

    1992-10-01

    The BCG vaccine has been used to prevent tuberculosis since 1921 and applied for immunostimulation in neoplasia since the 1960s. Both the preventive and immunostimulation effects have been evaluated and communicated with contradictory, positive and negative conclusions. For an objective evaluation and interpretation of the protective efficacy, effectiveness and efficiency of the BCG vaccination it must be considered that: (1) several BCG substrains have been developed in manufacturing laboratories that differ in the residual virulence which determines immunogenicity and reactogenicity; (2) various liquid and freeze-dried BCG vaccine production methods are used, resulting in different BCG viable units per dose; (3) quantitative bioassay methods are not yet being used for statistical quality control of the vaccine; (4) BCG products are applied in various demographical, epidemiological and socioeconomic conditions with different vaccination policies; (5) inadequate biostatistical models are often used to analyse efficacy, effectiveness and adverse reactions. The same conditions influence the precise evaluation of BCG immunostimulation in neoplasia. Recombinant DNA technology will modify production methods, and explain at the molecular level the mechanism of the protective effects BCG confers in tuberculosis and immunostimulation in neoplasia. High level laboratory techniques and biostatistical methods, based on probability logic and inductive inference, ensure appropriate experimental designs and the exact analysis of laboratory data and the results of vaccination policies. They will lead to the evaluation of the protective effect of BCG in order to reduce the BCG contradictions. PMID:1493232

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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....

  3. Extensive Mycobacterium bovis BCG Infection of Liver Parenchymal Cells in Immunocompromised Mice

    OpenAIRE

    Mills, John W.; Ryan, Lynn; LaCourse, Ronald; North, Robert J.

    2001-01-01

    A histologic study was performed on the livers of wild-type (WT), severe combined immunodeficient (SCID), hydrocortisone acetate (HC)-treated WT, and HC-treated SCID mice infected intravenously with 105 CFU of Mycobacterium bovis BCG. It was found that infection progressed faster in SCID mice than in WT mice and that HC treatment caused exacerbation of infection in both types of mice. In all cases infection in the liver was confined to granulomas that were populated predominantly by macrophag...

  4. 腹膜播種に対するBCG. Levamisole免疫療法

    OpenAIRE

    小林, 征二

    1983-01-01

    BCG and levamisole (LMS) immunotherapies were applied to an experimental model of cancer in the digestive organs by considering the abdominal wall as the intestinal tract wall. Ehrlich ascites tumor cells transplanted subcutaneously into the abdominal wall of mice invaded to the parietal peritoneum in approximately two weeks. Afterwards the tumor cells appeared in the peritoneal cavity, following retention of ascites. Almost all tumor bearing mice died within three weeks after the appearance ...

  5. 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.

  6. Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination.

    Science.gov (United States)

    Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

    2015-01-01

    Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history of exposure to tuberculosis. Innovative methodology to access the unusual L-form elements derived from human blood was developed. The methodology outlines the path of transformation of non- cultivable L-form element to cultivable bacteria and their adaptation for growth in vitro. All isolates showed typical L-forms growth features ("fried eggs" colonies and biofilm). Electron microscopy revealed morphology evidencing peculiar characteristics of bacterial L-form population (cell wall deficient polymorphic elements of variable shape and size). Regular detection of acid fast bacteria in smears of isolated blood L-form cultures, led us to start their identification by using specific Mycobactrium spp. genetic tests. Forty five of 97 genetically tested blood cultures provided specific positive signals for mycobacteria, confirmed by at least one of the 3 specific assays (16S rRNA PCR; IS6110 Real Time PCR and spoligotyping). In conclusion, the obtained genetic evidence suggests that these L-forms are of mycobacterial origin. As the investigated people had been vaccinated with BCG, we can assume that the identified mycobacterial L-forms may be produced by persisting live BCG vaccine. PMID:25874947

  7. Attenuated Host Resistance against Mycobacterium bovis BCG Infection in Mice Lacking Osteopontin

    OpenAIRE

    Nau, Gerard J.; Liaw, Lucy; Chupp, Geoffrey L.; Berman, Jeffrey S.; Hogan, Brigid L.M.; Young, Richard A.

    1999-01-01

    Expression of the cytokine osteopontin (OPN) is elevated in granulomas caused by Mycobacterium tuberculosis. We tested the hypothesis that OPN contributes to host protection in a mouse model of mycobacterial infection. When infected with Mycobacterium bovis BCG, mice lacking a functional OPN gene had more severe infections characterized by heavier bacterial loads and a delayed clearance of the bacteria. The OPN-null mice had greater granuloma burdens consistent with the elevated bacterial loa...

  8. 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.

  9. 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.

  10. 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.

  11. A Novel Accessory Molecule Trim59 Involved in Cytotoxicity of BCG-Activated Macrophages

    OpenAIRE

    Zhao, Xiangfeng; Liu, Qihui; Du, Baiqiu; Li, Peng; Cui, Qu; Han, Xiao; Du, Bairong; Yan, Dongmei; Zhu, Xun

    2012-01-01

    BCG-activated macrophages (BAM) could kill the tumor cells through cell-cell contact. In this process membrane proteins play an important role. However, up to date, few membrane proteins were revealed. In this study, we selected a surface molecule named Trim59, which was specifically expressed on BAM membrane (compared with the negative control). We cloned and prokaryoticly expressed the extracellular domain of Trim59, purified the recombinant protein and generated polyclonal antibodies. Immu...

  12. 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.

  13. 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

  14. 江西省2005~2008年疑似预防接种异常反应监测系统运转情况及监测结果 分析%Analysis on the Running Situation and Results of Surveillance System of Adverse Events Following Immunization in Jiangxi Province, during 2005-2008

    Institute of Scientific and Technical Information of China (English)

    王东海; 涂秋凤; 郭世成; 成慧; 姚瑶

    2011-01-01

    reported by township hospitals and county center for disease control and prevention (CDC ). The proportions of AEFIs reported within 24 hours and that investigated within 48 hours after reporting was 48.21% and 78.57% respectively. The ratio between male and female was 211. 71. 43% AEFI cases related to the NIP vaccines. The AEFI cases occurring within 24 hours, 48hours, and 2-7days were 51.79%, 16.07% and 17.26% respectively. Over 1/3 clinical diagnosis of AEFI are sclerosis, swelling and a Aching, and sterile abscess. AEFIs mostly distributed in the following vaccines: diphtheria, tetanus and pertussis combined vaccine (DPT), Hepatitis B vaccine, and bacille Calmette-Guerin ( BCG). The 3 highest reported AEFI incidence rate were DPT, BCG, diphtheria and tetanus combined vaccine. Conclusions The overall timeliness and sensitivity of national AEFI surveillance system need to be improved. Building the compensation mechanism for the AEFI, and turning the AEFI systeminto a public open systems may be a feasible way toimprove the sensitivity of surveillance.

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

    International Nuclear Information System (INIS)

    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. (orig.)

  16. 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.

  17. 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

  18. CXCL16 participates in pathogenesis of immunological liver injury by regulating T lymphocyte infiltration in liver tissue

    Institute of Scientific and Technical Information of China (English)

    Huan-Bin Xu; Yan-Ping Gong; Jin Cheng; Yi-Wei Chu; Si-Dong Xiong

    2005-01-01

    AIM: To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism of T lymphocyte infiltration requlated by CXCL16.METHODS: Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide.Expression pattem and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis. Anti-CXCL16 antibody was administrated in vivo to investigate its effect on T-cell recruitment and acute hepatic necrosis. The survival of murine model was also evaluated.RESULTS: The murine immunological liver injury model was successfully established. CXCL16 expression increased and predominantly distributed in periportal areas and vascular endothelia in injured liver tissues. Administration of anti-CXCL16 Ab protected the mice from death and acute liver damage. Approximately 70% of the mice survived for 72 h in the anti-CXCL16 Ab treatment group, whereas 80% died within 72 h in control Ab group. The number of liver-infiltrating T lymphocytes was significantly reduced from 1.01×L07 to 3.52x 106/liver, compared with control Ab treatment.CONCLUSION: CXCL16 is involved in immunological liver injury by regulating T lymphocyte infiltration in liver tissue.

  19. Hipersensibilidade tuberculínica em crianças menores de um ano de idade vacinadas com BCG oral Tuberculinic hypersensibility among children under one year of life, vaccinated with BCG by oral administration

    Directory of Open Access Journals (Sweden)

    Roberto Brólio

    1977-03-01

    Full Text Available São relatados os resultados da pesquisa da hipersensibilidade tuberculínica pelo PPD, Rt-23,2UT, em crianças menores de um ano de idade, vacinadas anteriormente com BCG oral, pertencentes a uma área do município de São Paulo. Os resultados mostram que para 790 crianças houve 13,0% de reatores fracos e 16,3% de reatores fortes, com um total de 29,3% de reatores. São feitos comentários sobre a vacinação oral e o baixo percentual de reatores encontrados, no controle tuberculínico pós-vacinal, relativamente aos obtidos com o BCG intradérmico.Hypersensibility reaction to tuberculin (PPD RT-23 was studied during five years among children under one year of age, vaccinated with BCG by oral administration, living in an area of city S. Paulo, Brazil. Of 790 children, 13,0% showed a weak reaction and 16.4% showed a strong reaction, totalizing 29.4% reactors. Comparing the results of convertors after BCG vaccination by intradermic administration, this paper shows that a low percentage of children became convertors after being vaccinated with BCG by oral administration.

  20. Construction of recombinant plasmid pBCG-EmⅡ/3-10 of echinococcus multilocularis and its significance%多房棘球绦虫重组质粒BCG-EmⅡ/3-10的构建及意义

    Institute of Scientific and Technical Information of China (English)

    郭鄂平; 陈林; 张光玉

    2008-01-01

    目的:构建多房棘球绦虫重组质粒BCG-EmⅡ/3-1 0,探索泡球蚴病防治的新途径.方法:超声粉碎泡球蚴组织提取总RNA,通过RT-PCR扩增EmⅡ/3-10抗原编码基因,将该基因定向克隆到大肠埃希菌-分枝杆菌穿梭表达载体pBCG,构建重组质粒pBCG-EmⅡ/3-10,电穿孔法将该质粒导入BCG构建多房棘球绦虫重组BCG-EmⅡ/3-10.结果:经过PCR扩增鉴定、电泳证实获得的重组基因的大小和插入方向正确.结论:成功构建了多房棘球绦虫重组质粒BCG-EmⅡ/3-10,为进一步研究多房棘球绦虫重组疫苗奠定基础.

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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.

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

    Science.gov (United States)

    Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria

    2015-01-01

    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. PMID:26716832

  4. Removing ballistocardiogram (BCG artifact from full-scalp EEG acquired inside the MR scanner with Orthogonal Matching Pursuit (OMP

    Directory of Open Access Journals (Sweden)

    Hongjing eXia

    2014-07-01

    Full Text Available Ballistocardiogram (BCG artifact remains a major challenge that renders electroencephalographic (EEG signals hard to interpret in simultaneous EEG and functional MRI (fMRI data acquisition. Here, we propose an integrated learning and inference approach that takes advantage of a commercial high-density EEG cap, to estimate the BCG contribution in noisy EEG recordings from inside the MR scanner. To estimate reliably the full-scalp BCG artifacts, a near-optimal subset (20 out of 256 of channels first was identified using a modified recording setup. In subsequent recordings inside the MR scanner, BCG-only signal from this subset of channels was used to generate continuous estimates of the full-scalp BCG artifacts via inference, from which the intended EEG signal was recovered. The reconstruction of the EEG was performed with both a direct subtraction and an optimization scheme. We evaluated the performance on both synthetic and real contaminated recordings, and compared it to the benchmark Optimal Basis Set (OBS method. In the challenging non-event-related-potential (non-ERP EEG studies, our reconstruction can yield more than fourteen-fold improvement in reducing the normalized RMS error of EEG signals, compared to OBS.

  5. 结核病疫苗研究进展%Research progress in tuberculosis vaccines

    Institute of Scientific and Technical Information of China (English)

    杨明; 尹文; 汪爱勤

    2010-01-01

    At present, the epidemic of tuberculosis (TB) is severe, and the only available vaccine,Bacillus Calmette-Guerin (BCG), is not high efficacious.Thus, there is a need for the development of novel TB vaccines which are more safe, effective, practical and inexpensive.This review summarizes the advance in the development of TB vaccines, including recombinant BCG vaccine, live attenuated vaccine, subunit vaccine, DNA vaccine and viral vector vaccine.%目前结核病疫情非常严峻,而唯一可用的疫苗卡介苗效果并不理想.因此,需要研发更安全有效和实用价廉的新型疫苗.此文综述了目前正在研发的新型结核病疫苗的研究进展,这些疫苗包括重组卡介苗、减毒活疫苗、亚单位疫苗、DNA疫苗和病毒载体疫苗.

  6. Chemoprophylaxis in the vesical tumoral recurrence

    International Nuclear Information System (INIS)

    The superficial bladder tumors are characterized by a high rate of recurrence taking place especially within the first two years that is even higher in the high risk groups. There is an agreement in the usefulness of the Calmette-Guerin Bacillus (CGB) to diminish the tumoral recurrence. The intravesical chemotherapy with other medications have demonstrated its profit or not in decreasing the recurrence of these bladder tumors. Between 1999 and 2008 we studied and treated 110 patients (96 men and 14 women), aged in average 63 years old. They were divided into three groups for the treatment of the tumoral recidivism after the transurethral resection or partial cystectomy, using three different chemoprophylactic agents and inmunomodulators (Thio-Tepa, BCG+Transference Factor, Doxorubicin +Interferon Alpha 2b). The objective of this research was presenting our experience in the treatment of these patients during five years, obtaining better results in the group treated with doxorubicin + interferon alpha 2b, followed by the group treated by means of BCG + transference factor, with a remarked decrease of the recurrence and a limitation in the long term progression of the disease

  7. High-Risk Non-Muscle-Invasive Bladder Cancer-Therapy Options During Intravesical BCG Shortage.

    Science.gov (United States)

    Veeratterapillay, Rajan; Heer, Rakesh; Johnson, Mark I; Persad, Raj; Bach, Christian

    2016-09-01

    Bladder cancer is the second commonest urinary tract malignancy with 70-80 % being non-muscle invasive (NMIBC) at diagnosis. Patients with high-risk NMIBC (T1/Tis, with high grade/G3, or CIS) represent a challenging group as they are at greater risk of recurrence and progression. Intravesical Bacilli Calmette-Guerin (BCG) is commonly used as first line therapy in this patient group but there is a current worldwide shortage. BCG has been shown to reduce recurrence in high-risk NMIBC and is more effective that other intravesical agents including mitomycin C, epirubicin, interferon-alpha and gemcitabine. Primary cystectomy offers a high change of cure in this cohort (80-90 %) and is a more radical treatment option which patients need to be counselled carefully about. Bladder thermotherapy and electromotive drug administration with mitomycin C are alternative therapies with promising short-term results although long-term follow-up data are lacking.

  8. HAEMATOLOGICAL PROFILE FOLLOWING IMMUNOMODULATION DURING LATE GESTATION IN BUFFALOES (BUBALIS BUBALUS

    Directory of Open Access Journals (Sweden)

    Z.I, Qureshi, L.A. Lodhi, H.A. Samad, N.A. Naz1 and M. Nawaz

    2001-07-01

    Full Text Available Thirty-two adult riverine buffaloes (Buhalis bubalus in their last trimester of pregnancy were selected and randomly divided into four groups. The buffaloes of group I served as control. Animals in group II, III and IV were treated twice (7 days apart with levamisole hydrochloride (0.5mg/kg b. w. orally, Etosol (Vit E+Se, 10ml, I/m and Bacilli Calmette Guerine (BCG (0.5 ml/animal, s/c, respectively. Blood samples were collected at weekly intervals starting day 0 untill parturition. Total erythrocytic count and packed cell volume values were higher (P<0.05 in levamisole and vit E+Se treated group of buffaloes. Haemoglobin concentration was higher (P<0.05 inVit E+Se treated group. MCV, MCH and MCHC remained unchanged among all the experimental groups. Total leukocyte count was higher (P<0.05 in levamisole treated group of buffaloes. Differential leukocyte counts (relative revealed moderate lymphocytosis in all immunomodulated groups with significantly higher counts in Vit E+Se treated buffaloes. It was inferred that levamisole and vit E-se altered some haematological values, whereas BCG did not affect the haematological parameters.

  9. Effects of tumor necrosis factor-alpha and interferon-gamma on expressions of matrix metalloproteinase-2 and -9 in human bladder cancer cells.

    Science.gov (United States)

    Shin, K Y; Moon, H S; Park, H Y; Lee, T Y; Woo, Y N; Kim, H J; Lee, S J; Kong, G

    2000-10-31

    We have investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon (INF-gamma), the potent Bacillus Calmette-Guerin (BCG)-induced cytokines on the production of MMP-2, MMP-9, TIMP-1, TIMP-2 and MT1-MMP in high grade human bladder cancer cell lines, T-24, J-82 and HT-1376 cell lines. MMP-2 expression and activity were decreased in T-24 cells treated with both cytokines in a dose dependent manner. However, J-82 cells treated with TNF-alpha and INF-gamma revealed dose dependent increases of MMP-9 expression and activity with similar baseline expression and activity of MMP-2. HT-1376 cells after exposure to TNF-alpha only enhanced the expression and activity of MMP-9. These results indicate that TNF-alpha and INF-gamma could regulate the production of MMP-2 or MMP-9 on bladder cancer cells and their patterns of regulation are cell specific. Furthermore, this diverse response of bladder cancer cells to TNF-alpha and INF-gamma suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs.

  10. A combined DNA vaccine provides protective immunity against Mycobacterium bovis and Brucella abortus in cattle.

    Science.gov (United States)

    Hu, Xi-Dan; Yu, Da-Hai; Chen, Su-Ting; Li, Shu-Xia; Cai, Hong

    2009-04-01

    We evaluated the immunogenicity and protective efficacy of a combined DNA vaccine containing six genes encoding immunodominant antigens from Mycobacterium bovis and Brucella abortus. The number of lymph node and spleen cultures positive for M. bovis and B. abortus from calves immunized with the combined DNA vaccine was significantly reduced (p abortus 544. The combined DNA vaccine group displayed stronger antigen-specific interferon-gamma (IFN-gamma) responses and antigen-specific IFN-gamma ELISPOT activities 2 months after final immunization and after challenge. Antigen-specific CD4(+) and CD8(+) T cell responses in the combined DNA vaccine group were higher than either the Bacillus Calmette-Guerin (BCG)-positive or S19-positive control group. Likewise, more calves in the DNA vaccine group exhibited antigen-specific IgG titers and had higher IgG titers than those in the BCG- or S19-immunized groups 2 months after the final immunization. Moreover, two antigens in the combined DNA vaccine induced significant antigen-specific IFN-gamma responses 6 months after challenge (p S19 against B. abortus. This is the first report to demonstrate that a single combined DNA vaccine protects cattle against two infectious diseases. PMID:19364278

  11. Observation on protection by immunization with mix recombinant BCG-Em Ⅱ/3 and BCG-Em14-3-3 vaccine of echinococcus multilocularis%多房棘球绦虫混合重组BCG-EmⅡ/3和BCG-Em14-3-3疫苗诱导的保护力观察

    Institute of Scientific and Technical Information of China (English)

    蒋光琼; 李文桂; 王鸿; 朱佑明

    2008-01-01

    目的:探讨多房棘球绦虫(Echinococcus multilocularis,Em)混合重组BCC-EmⅡ/3和BCG-Em14-3-3疫苗免疫小鼠后对Em原头节攻击感染的保护性作用.方法:将混合重组BCG疫苗采用皮下注射和鼻腔内接种分别免疫BALB/c鼠,免疫后8周用多房棘球绦虫原头节进行攻击感染,感染后18周剖杀小鼠,计算减蚴率,测定血清中IgG及其亚类和IgE水平,同时设有空载体、BCG和PBS对照.结果:混合疫苗接种组的减蚴率为45.29%~76.47%,血清IgG、IgG2a、IgG2b和lgE水平明显升高,IgG1和IgG3显著降低.结论:多房棘球绦虫混合重组BCG-EmⅡ/3和BCG-Em14-3-3疫苗鼻腔内接种是一种较好的途径,IgG、IgG2a、IgG2b和IgE在疫苗诱导的保护力中起重要作用.

  12. 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.

  13. 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.

  14. 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

    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...

  15. 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.

  16. 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.

  17. 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.

  18. BCG Moreau Rio de Janeiro: an oral vaccine against tuberculosis - review

    OpenAIRE

    Thereza Christina Benévolo-de-Andrade; Renata Monteiro-Maia; Catherine Cosgrove; Luiz Roberto R Castello-Branco

    2005-01-01

    The vaccine Bacillus of Calmette Guérin (BCG) was originally developed in France as an oral vaccine against tuberculosis. The oral use of this vaccine was replaced by the parenteral route in almost all countries after the Lubeck disaster. In contrast, Brazil retained the oral delivery of the vaccine until the mid-seventies when it was replaced by the intradermal route. This change in route of delivery was mainly secondary to pressure by medical practitioners based on the poor responses of ora...

  19. BCG: a computer code for calculating neutron spectra and criticality in cells of fast reactors

    International Nuclear Information System (INIS)

    The BCG code for determining the space and energy neutron flux distribution and criticality of fast reactor cylindrical cells is discussed. The code solves the unidimensional neutron transport equation together with interface current relations at each energy point in an unionized energy grid prepared for the cell and at an arbitrary number of spatial zones. While the spatial resolution is user specified, the energy dependence of the flux distribution is resolved according to the degree of variation in the reconstruced total microscopic cross sections of the atomic species in the cell. Results for a simplified fuel cell illustrate the high resolution and accuracy that can be obtained with the code. (author)

  20. 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)

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

    2016-01-01

    vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations. RESULTS: Among the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional...

  1. Molecular profiling of Mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme Rv3378c

    NARCIS (Netherlands)

    Layre, Emilie; Lee, Ho Jun; Young, David C.; Martinot, Amanda Jezek; Buter, Jeffrey; Minnaard, Adriaan J.; Annand, John W.; Fortune, Sarah M.; Snider, Barry B.; Matsunaga, Isamu; Rubin, Eric J.; Alber, Tom; Moody, D. Branch

    2014-01-01

    To identify lipids with roles in tuberculosis disease, we systematically compared the lipid content of virulent Mycobacterium tuberculosis with the attenuated vaccine strain Mycobacterium bovis bacillus Calmette-Guerin. Comparative lipidomics analysis identified more than 1,000 molecular differences

  2. Improved protection in guinea pigs after vaccination with a recombinant BCG expressing MPT64 on its surface

    Directory of Open Access Journals (Sweden)

    Simon O. Clark

    2015-01-01

    Full Text Available The lack of an efficient vaccine against tuberculosis is still one of the major problems threatening global human health. In previous work we showed that expression of the protective antigen MPT64 on the surface of Mycobacterium bovis BCG, the only approved vaccine against tuberculosis, strongly improved its immunogenicity and protective potential in mice. In this work we demonstrate that the same recombinant strain is able to induce better protection than wild type BCG also in guinea pigs preventing Mycobacterium tuberculosis dissemination and lung pathology, making this strain a strong candidate for further testing.

  3. 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.

  4. 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

    Objectives To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. Design Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. Study eligibility criteria Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. Data sources Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. Results Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies

  5. 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

    Directory of Open Access Journals (Sweden)

    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

  6. 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.

  7. The XXL survey XV: Evidence for dry merger driven BCG growth in XXL-100-GC X-ray clusters

    Science.gov (United States)

    Lavoie, S.; Willis, J. P.; Démoclès, 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.

    2016-08-01

    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 ≲ 1 in the XXL 100 brightest cluster sample. We use the global red sequence, Hα 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 cluster scale merger event, the BCG stellar mass lags behind the expected value from the Mcluster - MBCG relation but subsequently accretes stellar mass via dry mergers as the BCG and cluster evolve towards a relaxed state.

  8. 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 ...

  9. Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

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

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    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.

  12. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

    Directory of Open Access Journals (Sweden)

    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.

  13. The mycobacterial DNA-binding protein 1 (MDP1 from Mycobacterium bovis BCG influences various growth characteristics

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. Local skin reaction following an accidental injection from a BCG vaccine in a healthcare worker

    Directory of Open Access Journals (Sweden)

    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.

  16. EFISIENSI PERSAINGAN BANK UMUM SYARIAH: PENDEKATAN DATA ENVELOPMENT ANALYSIS (DEA DAN BOSTON CONSULTING GROUP (BCG

    Directory of Open Access Journals (Sweden)

    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

  17. 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.

  18. 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)

  19. 235例肺外结核性创面患者流行病学调查%Epidemiological investigation of 235 patients with extra-pulmonary tuberculosis wounds

    Institute of Scientific and Technical Information of China (English)

    常娜; 贾赤宇; 刘真; 张亚洁; 李文婷; 田甜

    2015-01-01

    目的 初步探讨肺外结核性创面流行病学特点和规律,为临床研究提供可靠数据.方法 对笔者单位2010年1月-2012年12月收治的肺外结核性创面患者的性别、年龄、民族、家庭背景、卡介苗接种情况、原发病灶、外伤史这几项资料进行回顾性分析,总结其规律及特点. 结果 5 863例肺外结核病患者中,235例出现结核性创面,占4.0%.其中男139例、女96例,男女之比为1.4∶1.0.年龄1~87(37±18)岁,其中大于15岁且小于或等于30岁青壮年患者构成比最大(100例,42.6%).多数患者为汉族;仅有11例患者为少数民族,占4.7%.患者中163例来自农村,占69.4%;72例来自城镇,占30.6%.卡介苗接种率为13.6%(32例).原发病灶中,以周围淋巴结结核为主,共112例,占47.7%,其中又以颈部淋巴结结核为主(99例,88.4%).21例(男19例、女2例)患者近期有车祸等外伤史. 结论 结核性创面有一定的发病率,并非罕见,以农村地区青壮年人群多发,患者的卡介苗接种率较低,颈部淋巴结结核为主要原发病灶.%Objective To investigate the epidemiological characteristics and patterns of extra-pulmonary tuberculosis wounds in order to provide reliable data for further clinical research.Methods Records of patients with extra-pulmonary tuberculosis wounds hospitalized from January 2010 to December 2012 were retrospectively analyzed,including gender,age,nationality,family background,Bacille CalmetteGuerin (BCG) vaccination,primary lesion,and history of injury.Results Tuberculosis wounds were found in 235 patients among 5 863 patients with extra-pulmonary tuberculosis,accounting for 4.0%.Among the patients with tuberculosis wounds,there were 139 male and 96 female,and the ratio of male to female was 1.4∶ 1.0.The age of patients ranged from 1 to 87 (37 ± 18) years old,and the highest incidence occurred in patients older than 15 and younger than or equal to 30 years old (100 cases

  20. Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Zhou Xing

    Full Text Available BACKGROUND: Recombinant adenovirus-vectored (Ad tuberculosis (TB vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. METHODS AND FINDINGS: Specific pathogen-free guinea pigs were immunized with BCG, AdAg85A intranasally (i.n, AdAg85A intramuscularly (i.m, BCG boosted with AdAg85A i.n, BCG boosted with AdAg85A i.m, or treated only with saline. The animals were then infected by a low-dose aerosol of M. tuberculosis (M.tb. At the specified times, the animals were sacrificed and the levels of infection in the lung and spleen were assessed. In separate studies, the long-term disease outcome of infected animals was monitored until the termination of this study. Immunization with Ad vaccine alone had minimal beneficial effects. Immunization with BCG alone and BCG prime-Ad vaccine boost regimens significantly reduced the level of M.tb infection in the tissues to a similar extent. However, while BCG alone prolonged the survival of infected guinea pigs, the majority of BCG-immunized animals succumbed by 53 weeks post-M.tb challenge. In contrast, intranasal or intramuscular Ad vaccine boosting of BCG-primed animals markedly improved the survival rate with 60% of BCG/Ad i.n- and 40% of BCG/Ad i.m-immunized guinea pigs still surviving by 74 weeks post-aerosol challenge. CONCLUSIONS: Boosting, particularly via the intranasal mucosal route, with AdAg85A vaccine is able to significantly enhance the long-term survival of BCG-primed guinea pigs following pulmonary M.tb challenge. Our results thus support further evaluation of this viral-vectored TB vaccine in clinical trials.

  1. 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

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

    OpenAIRE

    Ting-Yu Angela Liao; Alice Lau; Sunil Joseph; Vesa Hytönen; Zakaria Hmama

    2015-01-01

    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 deve...

  3. 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

  4. 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

  5. Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Billeskov, Rolf; Grandal, Michael V; Poulsen, Christian;

    2010-01-01

    vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4(+) T-cell specific TB10.4 epitope-pattern, which differed completely from...... that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments...... revealed that both TB10.4 and BCG were transported to Lamp(+)-compartments. BCG and TB10.4 however, were directed to different types of Lamp(+)-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely...

  6. 疫苗相关麻痹型脊灰病例死亡1例

    Institute of Scientific and Technical Information of China (English)

    郝振忠

    2011-01-01

    1 病例摘要 患儿,男,2006-05-02出生,第一胎,剖腹产,发育及体重正常.父母体健,否认家族疾病史.该患儿属于本地常住儿童,生前无外出史.该儿童于出生当日接种乙型肝炎疫苗(Hepatitis B Vaccine,HepB)第1针;2006-06-19接种HepB第2针、卡介苗(Bacillus Calmette Guerin,BCG)1针次;2006-07-20口服脊髓灰质炎减毒活疫苗(Oral Poliomyelitis Attenuated Live Vaccine,OPV)第1剂,2006-08-20接种OPV 第2剂(北京天坛生物制品股份有限公司生产,批号2005111111,有效期至2007年11月)、接种百日咳-白喉-破伤风联合疫苗(Diphtheria,Tetanus,Pertussis Combined Vaccine;DTP)第1针. 该患儿于2006-08-20接种OPV第2剂,半月后于2006-09-05出现发热(当时体温38℃)、恶心、呕吐、腹泻,双下肢无力.

  7. Mechanisms of immunological eradication of a syngeneic guinea pig tumor. II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity

    International Nuclear Information System (INIS)

    The influence of methotrexate on the development of immunity to the line 10 hepatoma was studied in guinea pigs. Chronic methotrexate treatment had no apparent effect on the ability of immune guinea pigs to suppress the growth of inoculated tumor cells. In contrast, the same methotrexate regimen inhibited the development of tumor immunity if started before the 8th day after immunization with a vaccine containing viable line 10 cells admixed with Bacillus Calmette-Guerin (BCG) cell walls. Thus, methotrexate selectively inhibited the afferent limb of the immune response. In adoptive transfer experiments, methotrexate-treated recipient guinea pigs were capable of being passively sensitized with immune spleen cells, indicating that the primary cell-mediated immune response of the recipient was not required for adoptive immunity. The contribution of recipient T cells in adoptive immunity was further investigated in guinea pigs deleted of T cells by thymectomy, irradiation, and bone marrow reconstitution. Despite demonstrable deficiency in T lymphocyte reactions, B animals were fully capable of rejecting tumors after transfer of immune cells. These results suggest that the expression of adoptive immunity was independent of recipient T cell participation. In addition, sublethal irradiation of immune spleen cells prior to adoptive transfer abolished their efficacy. Proliferation of transferred immune cells in the recipient may be essential for expression of adoptive immunity

  8. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer.

    Science.gov (United States)

    Hojeij, Rim; Domingos-Pereira, Sonia; Nkosi, Marianne; Gharbi, Dalila; Derré, Laurent; Schiller, John T; Jichlinski, Patrice; Nardelli-Haefliger, Denise

    2016-01-01

    Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC) and it is amenable to local treatments, with intravesical (IVES) Bacillus-Calmette-Guerin (BCG) immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV) can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK) combined to Ganciclovir (GCV) led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC. PMID:27428950

  9. Adjuvant therapy of malignant melanoma.

    Science.gov (United States)

    Molife, R; Hancock, B W

    2002-10-01

    High risk surgically resected melanoma is associated with a less than 50% 5-year survival. Adjuvant therapy is an appropriate treatment modality in this setting, and is more likely to be effective as the tumour burden here is small. Clinical observations of spontaneous tumour regressions and a highly variable rate of disease progression suggest a role of the immune system in the natural history of melanoma. Biological agents have therefore been the subjects of numerous adjuvant studies. Early, randomised controlled trials (RCTs) of Bacillus Calmette-Guerin (BCG), levamisole, Corynebacterium parvum, chemotherapy, isolated limb perfusion (ILP), radiotherapy, transfer factor (TF), megestrol acetate and vitamin A yielded largely negative results. Current trials focus on vaccines and the interferons. To date the latter is the only therapy to have shown a significant benefit in the prospective randomised controlled phase III setting. This report represents a systematic review of studies in adjuvant therapy in melanoma. Data from ongoing studies is awaited before a role for adjuvant agents in high risk melanoma is confirmed. PMID:12399001

  10. Adjuvant therapy of melanoma.

    Science.gov (United States)

    Agarwala, S S; Kirkwood, J M

    1998-06-01

    Patients with AJCC Stage IIB and III melanoma have a poor 5-year survival rate which has been the driving force behind attempts to find an effective adjuvant therapy for this stage of disease that would effectively reduce relapse and improve survival. Immunotherapy with bacillus Calmette-Guerin (BCG), Corynebacterium parvum, and levamisole have not been successful in achieving this goal, nor have trials with chemotherapy in the adjuvant setting, including high-dose chemotherapy with autologous bone marrow transplantation. The recent Eastern Cooperative Oncology Group (ECOG) 1684 study showed significant improvement in relapse-free and overall survival with high doses of alpha interferon (IFNalpha) given for 1 year. Lower dosages of IFNalpha have to date been unsuccessful in impacting upon long-term survival. Recent data with vaccines have been encouraging, and the GM2-KLH vaccine is the focus of ongoing intergroup study comparing this treatment with IFNalpha in resected Stage IIB and III melanoma. The various regimens are reviewed in this article. PMID:9588723

  11. Síntese e avaliação farmacológica de N’-benzilideno-cumarinas-3-carboidrazidas frente ao Mycobacterium causador da tuberculose

    Directory of Open Access Journals (Sweden)

    Felipe R. Vicente

    2010-04-01

    Full Text Available This article describes a series of twenty-one N’-benzylidene-2-oxo-2H-chromene-3-carbohydrazides (5a-5v which were synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test (MABA and the activity expressed as the minimum inhibitory concentration (MIC in μg/mL. Afterwards, the compounds which showed antitubercular activity (50-100 μg/mL 5c, 5g, 5h, 5j, 5l, 5p and 5t were evaluated for their cell viabilities in macrophages infected and non infected with Mycobacterium bovis Bacillus Calmette-Guerin (BCG. The compounds 5c, 5g, 5h, 5j, 5l were not cytotoxic in their respective MIC values, indicating that these compounds could be considered a good starting point to further studies aiming to develop a new lead compound to treat multidrug-resistant tuberculosis (TB-MDR/XDR.

  12. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Rim Hojeij

    2016-07-01

    Full Text Available Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC and it is amenable to local treatments, with intravesical (IVES Bacillus-Calmette-Guerin (BCG immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK combined to Ganciclovir (GCV led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC.

  13. Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Mustafa, A S; Amoudy, H A; Wiker, H G;

    1998-01-01

    We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (r......GroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well...... as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN...

  14. Characterization of the fibronectin-attachment protein of Mycobacterium avium reveals a fibronectin-binding motif conserved among mycobacteria.

    Science.gov (United States)

    Schorey, J S; Holsti, M A; Ratliff, T L; Allen, P M; Brown, E J

    1996-07-01

    Mycobacterium avium is an intracellular pathogen and a major opportunistic infectious agent observed in patients with acquired immune deficiency syndrome (AIDS). Evidence suggests that the initial portal of infection by M. avium is often the gastrointestinal tract. However, the mechanism by which the M. avium crosses the epithelial barrier is unclear. A possible mechanism is suggested by the ability of M. avium to bind fibronectin, an extracellular matrix protein that is a virulence factor for several extracellular pathogenic bacteria which bind to mucosal surfaces. To further characterize fibronectin binding by M. avium, we have cloned the M. avium fibronectin-attachment protein (FAP). The M. avium FAP (FAP-A) has an unusually large number of Pro and Ala residues (40% overall) and is 50% identical to FAP of both Mycobacterium leprae and Mycobacterium tuberculosis. Using recombinant FAP-A and FAP-A peptides, we show that two non-continuous regions in FAP-A bind fibronectin. Peptides from these regions and homologous sequences from M. leprae FAP inhibit fibronectin binding by both M. avium and Mycobacterium bovis Bacillus Calmette-Guerin (BCG). These regions have no homology to eukaryotic fibronectin-binding proteins and are only distantly related to fibronectin-binding peptides of Gram-positive bacteria. Nevertheless, these fibronectin-binding regions are highly conserved among the mycobacterial FAPs, suggesting an essential function for this interaction in mycobacteria infection of their metazoan hosts.

  15. Hepato-protective Effect of Polysaccharides Extracted from Inula Britannica Flower for Mice

    Institute of Scientific and Technical Information of China (English)

    HONG Tie; DONG Man; GAO Yan; ZHAO Jing; WU Yi

    2012-01-01

    The polysaccharides extracted from Inula britannica flower(IBP) exhibited a significant anti-liver injury activity.The properties and chemical compositions of IBP were analyzed via high performance liquid chromatography(HPLC) and infrared spectroscopy(IR) methods.The results show that the molecular weight distribution of IBP is from 600 to 3500.The weight-average molecular weight is 1099.IBP consists of mannose,glucuronic acid,rhamnose,galacturonic acid,glucose,galactose and arabinose with a molar ratio of 4.1:1:1.4:2.7:14.6:6.3:7.9.The IR spectrum of IBP reveals the typical characteristics of polysaccharides and proteins.After administration of IBP with 100,50 and 25 mg/kg body mass to liver injury mice induced by CCl4 or bacillus calmette guerin-lipopolysaccharide (BCG-LPS),not only the blood alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels decreased significantly(P<0.05),but aslo the liver tissue malondialdehyde(MDA) level decreased significantly(P<0.01).The superoxide dismutase(SOD) level increased significantly(P<0.01).IBP shows significant anti-liver injury and antioxidation activity.

  16. The role of the mycobacterial DNA-binding protein 1 (MDP1 from Mycobacterium bovis BCG in host cell interaction

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    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.

  17. 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.

  18. 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(100 μ L) 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,100 μL 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 of8 to 13 weeks.At the age of 7-13 weeks,mice in Group A and Group D were treated with 100 μL 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 for7 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-I2 and IFN- γ in 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- γ proteins.After IIK 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(P<0.05),and there was no significant difference between Group B and C(P>0.05);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

  19. ICM cooling, AGN feedback and BCG properties of galaxy groups-Five properties where groups differ from clusters

    CERN Document Server

    Bharadwaj, V; Schellenberger, G; Eckmiller, H J; Mittal, R; Israel, H

    2014-01-01

    Using Chandra data for a sample of 26 galaxy groups, we constrained the central cooling times (CCTs) of the ICM and classified the groups as strong cool-core (SCC), weak cool-core (WCC) and non-cool-core (NCC) based on their CCTs. The total radio luminosity of the brightest cluster galaxy (BCG) was obtained using radio catalog data and literature, which was compared to the CCT to understand the link between gas cooling and radio output. We determined K-band luminosities of the BCG with 2MASS data, and used it to constrain the masses of the SMBH, which were then compared to the radio output. We also tested for correlations between the BCG luminosity and the overall X-ray luminosity and mass of the group. The observed cool-core/non-cool-core fractions for groups are comparable to those of clusters. However, notable differences are seen. For clusters, all SCCs have a central temperature drop, but for groups, this is not the case as some SCCs have centrally rising temperature profiles. While for the cluster sampl...

  20. Medroxyprogesterone acetate alters Mycobacterium bovis BCG-induced cytokine production in peripheral blood mononuclear cells of contraceptive users.

    Directory of Open Access Journals (Sweden)

    Léanie Kleynhans

    Full Text Available Most individuals latently infected with Mycobacterium tuberculosis (M.tb contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstrated both glucocorticoid and progestogenic properties at saturating and pharmacological concentrations in peripheral blood mononuclear cells (PBMCs and suppressed antigen specific cytokine production. Furthermore we showed that PBMCs from women using MPA produced significantly lower levels of IL-1α, IL-12p40, IL-10, IL-13 and G-CSF in response to BCG which corresponded with lower numbers of circulating monocytes observed in these women. Our research study is the first to show that MPA impacts on infections outside the genital tract due to a systemic effect on immune function. Therefore MPA use could alter susceptibility to TB, TB disease severity as well as change the efficacy of new BCG-based vaccines, especially prime-boost vaccine strategies which may be administered to adult or adolescent women in the future.

  1. 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.

  2. 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。

  3. 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.

  4. 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

  5. HI in XMD Galaxies III. GMRT observations of BCG HS0822+3542

    CERN Document Server

    Chengalur, J N; Martin, J M; Kniazev, A Yu; Chengalur, Jayaram N.

    2006-01-01

    We present Giant Metrewave Radio Telescope (GMRT) HI 21-cm line data for the smallest known eXtremely Metal Deficient (XMD) blue compact galaxy (BCG) HS0822+3542. From HST imaging it has been suggested that HS0822+3542 actually consists of two still smaller (~ 100pc sized) ultra-compact dwarfs that are in the process of merging. The brighter of these two putative ultra compact dwarfs has an ocular appearance, similar to that seen in galaxies that have suffered a penetrating encounter with a smaller companion. From our HI imaging we find that the gas distribution and kinematics in this object are similar to that of other low mass galaxies, albeit with some evidence for tidal disturbance. On the other hand, the HI emission has an angular size ~25 times larger than that of the putative ultra-compact dwarfs. The optical emission is also offset from the centre of the HI emission. HS0822+3542 is located in the Lynx-Cancer void, but has a nearby companion LSB dwarf galaxy SAO0822+3545. In light of all this we also c...

  6. Immunomodulation of Homeopathic Thymulin 5CH in a BCG-Induced Granuloma Model

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    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.

  7. Protective effect of mycelial polysaccharides from Cordyceps sinensis on immunological liver injury in mice

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    Kai-zhong DONG

    2016-04-01

    Full Text Available Objective  To explore the protective effects of mycelial polysaccharides from Cordyceps sinensis (MPCS on BCG+LPS-induced liver injury in mice. Methods  The immunological liver injury mice model was reproduced by giving bacillus Calmette-Guerin (BCG and lipopolysaccharide (LPS. Sixty NIH mice were randomly assigned into 6 groups (10 each: normal control group, model group, mycelium polysaccharide in high (100mg/kg, medium (50mg/kg and low (25mg/kg dose group, and bifendate (150mg/kg treatment group. The serum transaminase levels of alanine ALT and AST were assayed with ELISA, nitric oxide (NO in serum was measured by nitrate reductase method, and the liver homogenate was prepared for the determination of the contents of interleukin-1β(IL-1β and tumor necrosis factor-α(TNF-α. The mRNA expression levels of IL-6 and iNOS in hepatic tissue were assessed using RT-PCR . Results  In the mice of immunological liver injury, mycelial polysaccharides from Cordyceps sinensis obviously lowered the serum ALT and AST levels (P<0.01, high dose MPCS significantly reduced the serum NO and liver tissue IL-1βand TNF-αlevels (P<0.01. Compared with the model group, high and medium dose MPCS significantly reduced the expression levels of IL-6 and iNOS mRNA in hepatic tissues (P<0.01. Conclusion  MPCS shows a certain protective effect on immunological liver injury induced by BCG plus LPS in mice. DOI: 10.11855/j.issn.0577-7402.2016.04.05

  8. The response of variant histology bladder cancer to intravesical immunotherapy compared to conventional cancer

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    Ofer Nathan Gofrit

    2016-03-01

    Full Text Available Background: High-grade urothelial carcinomas (UC often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with Bacillus Calmette Guerin (BCG. We compared the response to treatment with BCG of UC containing glandular, squamous, nested and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade urothelial carcinoma. Methods: A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. 41 patients with Ta or T1, confirmed by 2nd look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation 13 patients with squamous differentiation, in 9 patients glandular differentiation was seen and in 7 patients nested variant. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly. Findings: Patients with variant tumors had similar clinical features to patients with conventional disease including: age, males to female ratio, stage, presence of Tis and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC including: 5-year recurrence-free survival (63.5% Vs. 71.5%, p=0.05, 5-year progression to≥T2 -free survival (60% Vs. 82.5%, p=0.002, 5-year disease-specific survival (73% Vs. 92.5%, p=0.0004 and overall survival (66% Vs. 89.5%, 0.05. Interpretation: A patient with variant bladder cancer treated with intra-vesical immunotherapy has a 27% chance of dying from this disease within 5-years compared to 7.5% for a patient with conventional high-grade UC.

  9. 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.

  10. 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.

  11. 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.

  12. Valor preditivo do teste tuberculínico padronizado em crianças vacinadas com BCG

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    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.

  13. 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.

  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. A nested case-control study on the influencing factors of tuberculosis among people living with HIV/AIDS in Hunan province%湖南省HIV/AIDS人群结核发病影响因素的巢式病例对照研究

    Institute of Scientific and Technical Information of China (English)

    陈梦施; 杨华林; 陈艳芳; 谭红专; 白丽琼; 张艳辉; 刘军; 李桂平

    2010-01-01

    Objective To determine the risk factors related to tuberculosis infection among people living with HIV/AIDS and to develop strategies for preventing the co-infection.Methods A 1:2matched nested case-control study was carried out to analyze the influencing factors of tuberculosis among people living with HIV/AIDS.Results 1018 people living with HIV/AIDS were followed up for one year with a total number of 736.75 person-years,among them 62 tuberculosis cases were diagnosed.The incidence density of tuberculosis among people living with HIV/AIDS was 8.42 persons per 100 person-years.Factors as education level(OR=0.483),vaccination history of Bacille Calmette Guerin(OR=0.561),CD_4~+ count T-lymphocyte(OR=0.356),unemployment(OR=1.976),living alone(OR=2.646),and smoking(OR=2.215)were significantly related to the prevalence of tuberculosis among people living with HIV/AIDS.Conclusion High education level,with vaccination history of Bacille Calmette Guerin and high level of CD_4~+ T-lymphocyte count were protective factors while being unemployed,living alone,and smoking habit were risk factors related to the prevalence of tuberculosis among people living with HIV/AIDS.%目的 探讨HIV/AIDS人群发生结核病的危险因素.方法 采用1:2匹配的巢式病例对照研究方法分析HIV/AIDS人群发生结核的危险因素.结果 对1018例未患结核的HIV/AIDS人群随访观察1年,累计观察736.75人年,共检查出结核病患者62例,HIV/AIDS人群结核病发病密度为8.42人/100人年(62人/736.75人年).文化程度(OR=0.483)、卡介苗接种史(OR=0.561)、CD_4~+T淋巴细胞数(OR=0.356)、无业(OR=1.976)、单身(OR=2.646)和吸烟(OR=2.215)等因素与HIV/AIDS人群发生结核病有关.结论 文化程度高、有卡介苗接种史和CD_4~+T淋巴细胞数高是HIV/AIDS人群患结核病的保护因素;无业、单身和吸烟是HIV/AIDS人群患结核病的危险因素.

  16. 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...

  17. Comparison of the effect of the viral paramunity-inducers BCG and levamisole on the growth of a radiation-induced transplanted osteosarcoma in mice

    International Nuclear Information System (INIS)

    Treatment with paramunity inducers Pind avi and Pind orf resulted in general in a smaller number of tumor takes as compared to BCG, Levamisol or untreated controls. Tumor growth curves were independent of treatment. Each experiment was replicated three times. A comparison of pooled results showed significant differences between Pind avi treatment and untreated controls for each level of tumor cells. When pooling levels of tumor cells and testing each replication separately there was a highly significant difference between Pind avi and controls and Pind orf and controls. BCG and Levamisole showed no significant difference to controls. Pind avi and Pind orf considerably raised the number of tumor cells needed to results in 50% takes. For BCG on the other hand less cells were needed. The TD50 with Levamisole was somewhat higher than the TD50 of controls. The formation of metastases was infrequent (0,65%), and only seen in lung tissue. (orig./MG)

  18. 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

  19. The XXL survey XV: Evidence for dry merger driven BCG growth in XXL-100-GC X-ray clusters

    OpenAIRE

    Lavoie, S.; Willis, J. P.; Democles, J.; Eckert, D; F. Gastaldello; Smith, G. P.; Lidman, C.; Adami, C.; Pacaud, F.; Pierre, M.; Clerc, N.; Giles, P.; Lieu, M.; Chiappetti, L.; Altieri, B.

    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...

  20. Comparison of interferon {gamma} release assays and conventional screening tests before tumour necrosis factor {alpha} blockade in patients with inflammatory arthritis.

    LENUS (Irish Health Repository)

    Martin, J

    2012-02-01

    OBJECTIVE: To compare the performance of two interferon gamma release assays (IGRAs) and conventional screening tests in patients with inflammatory arthritis undergoing screening for latent tuberculosis infection (LTBI) before treatment with anti-tumour necrosis factor alpha (anti-TNFalpha) compounds. METHODS: Successive patients were subjected to conventional LTBI screening, including a tuberculin skin test (TST). The T-SPOT.TB test was performed on all patients and the QuantiFERON-TB Gold test was performed on a large subset. The results of the IGRAs were compared with the results of conventional screening tests. RESULTS: A total 150 patients were evaluated. The majority (57.9%) had rheumatoid arthritis. Previous vaccination with Bacille Calmette-Guerin was confirmed in 82% of patients. No patient had received prior anti-TB treatment. A total of 57 patients (38.0%) had at least one positive conventional risk factor. In contrast, an unequivocally positive T-SPOT.TB test was seen in only 14\\/143 (9.8%). There was 98.2% agreement between the two IGRAs. Statistically significant associations were found between each of the IGRAs and both TST and risk history, but not chest x-ray (CXR). A positive IGRA result was significantly associated with increased age. TB was not reactivated in any patient during the follow-up period. Interpretation: This study suggests that IGRAs may be useful when screening for LTBI before anti-TNFalpha therapy in patients with immune-mediated inflammatory diseases. The observations reported here also highlight the inadequate performance of CXR as a marker of LTBI.

  1. IFN-γ release assay: a diagnostic assistance tool of tuberculin skin test in pediatric tuberculosis in China

    Institute of Scientific and Technical Information of China (English)

    SUN Lin; SHEN A-dong; YAN Hui-min; HU Ying-hui; JIAO Wei-wei; GU Yi; XIAO Jing; LI Hui-min; JIAO An-xia; GUO Ya-jie

    2010-01-01

    Background Prompt diagnosis of Mycobacterium tuberculosis (MTB) infection is an essential step in tuberculosis control and elimination. However, it is often difficult to accurately diagnose pediatric tuberculosis (TB). The tuberculin test (TST) may have a low specificity because of cross-reactivity with antigens present in Mycobacterium bovis bacillus Calmette-Guerin (BCG) and other mycobacteria, especially in China with a predominantly BCG-vaccinated population.Early-secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10), stand out as suitable antigens that induce an interferon-gamma (IFN-γ) secreting, T-cell-mediated immune response to infection. While,considered the higher costs and complexity of the IFN-γ release assay (TSPOT), we aimed to evaluate the TSPOT and TST test in the clinical diagnosis of pediatric tuberculosis and to establish a diagnostic process suitable for China.Methods The sensitivity and specificity of the assay were evaluated in total seventy four children with active tuberculosis and fifty one nontuberculous children with other disease, and then the results were compared with TST.Logistic regression models were used to identify variables that were associated with positive results for each assay. The independent variables included sex, age, birth place, vaccination history, close contract with an active TB patient.Results The sensitivity of TSPOT was higher than TST in active TB children with or without BCG vaccination, as well as in children with culture-confirmed TB. But the difference was not significant statistically. Combining results of the TSPOT and TST improved the sensitivity to 94.6%. Agreement of the TST and TSPOT was low (77.0%, k=0.203) in active TB patients. The difference in specificity between TSPOT and TST test was statistically significant (94.1% vs.70.6%, P=0.006). Specificity of the two tests in patients without prior BCG vaccination history was similar (80.0% vs.60.0%). The concordance

  2. Differential effects of Radix Paeoniae Rubra (Chishao on cytokine and chemokine expression inducible by mycobacteria

    Directory of Open Access Journals (Sweden)

    Li James

    2011-03-01

    Full Text Available Abstract Background Upon initial infection with mycobacteria, macrophages secrete multiple cytokines and chemokines, including interleukin-6 (IL-6, IL-8 and tumor necrosis factor-α (TNF-α, to mediate host immune responses against the pathogen. Mycobacteria also induce the production of IL-10 via PKR activation in primary human monocytes and macrophages. As an anti-inflammatory cytokine, over-expression of IL-10 may contribute to mycobacterial evasion of the host immunity. Radix Paeoniae Rubra (RPR, Chishao, a Chinese medicinal herb with potentials of anti-inflammatory, hepatoprotective and neuroprotective effects, is used to treat tuberculosis. This study investigates the immunoregulatory effects of RPR on primary human blood macrophages (PBMac during mycobacterial infection. Methods The interaction of Bacillus Calmette-Guerin (BCG with PBMac was used as an experimental model. A series of procedures involving solvent extraction and fractionation were used to isolate bioactive constituents in RPR. RPR-EA-S1, a fraction with potent immunoregulatory effects was obtained with a bioactivity guided fractionation scheme. PBMac were treated with crude RPR extracts or RPR-EA-S1 before BCG stimulation. The expression levels of IL-6, IL-8, IL-10 and TNF-α were measured by qPCR and ELISA. Western blotting was used to determine the effects of RPR-EA-S1 on signaling kinases and transcriptional factors in the BCG-activated PBMac. Results In BCG-stimulated macrophages, crude RPR extracts and fraction RPR-EA-S1 specifically inhibited IL-10 production while enhanced IL-8 expression at both mRNA and protein levels without affecting the expressions of IL-6 and TNF-α. Inhibition of BCG-induced IL-10 expression by RPR-EA-S1 occurred in a dose- and time-dependent manner. RPR-EA-S1 did not affect the phosphorylation of cellular protein kinases including MAPK, Akt and GSK3β. Instead, it suppressed the degradation of IκBα in the cytoplasm and inhibited the

  3. Dynamic observation on IgG and its subclasses and IgE in sera of mice by immunization with mixed recombinant of BCG-Em Ⅱ/3 and BCG-Em14-3-3 vaccine of Echinococcus multilocularis%多房棘球绦虫混合重组BCG-Em Ⅱ/3和BCG-Em14-3-3疫苗免疫小鼠后IgG及其亚类和IgE的动态观察

    Institute of Scientific and Technical Information of China (English)

    李文桂; 王鸿; 朱佑明; 杨梅

    2009-01-01

    Objective To dynamically observe changes of IgG, its subclasses and IgE in sera of mice by immunization with mixed recombinant of BCG-Em Ⅱ/3 and BCG-Em14-3-3 vaccine of Echinococcus multilocularis (Era). Methods Forty Balb/c mice of 12-14 week old and 20-25 g weight were intranasally vaccinated by the vaccine, 4 mice were killed randomly by the weight on 0,2,4,6,8,10,12,14,16 and 18 weeks of immunization respectively, sera were gathered from the eyeball to measure IgG, its subclasses and IgE by routine ELISA. Results Levels of IgG, IgG2a and IgG2b in the sera of mice increased obviously on 2-18 weeks, reached the highest level on 10, 4 and 4 weeks respectively, the value was 0.095±0.033,0.022±0.001,0.023±0.003 respectively, as compared with the value on 0 week(0.030±0.013,0.012±0.004,0.013±0.004), the difference being statistically significant(q=2.95,4.87,2.81 respectively, P < 0.01 or P < 0.05); levels of IgG1, IgG3 and IgE in the sera of mice decreased remarkably on 2-18 weeks,came to the lowest level on 4,2,6 weeks respectively, the value was 0.031±0.004,0.136±0.002,0.114±0.002 respectively, as compared with the value on 0 week(0.192±0.007, 0.175±0.013,0.024±0.003), the difference being statistically significant (q =5.16,4.93,5.32 respectively, P < 0.01 or P < 0.05). Conclusion Helper T cell(TH) Ⅰ response is induced in mice by mixed recombinant of BCG-Em Ⅱ/3 and BCG-Em14-3-3 vaccine on early immunization.%目的 动态观察多房棘球绦虫混合重组BCG-Em Ⅱ/3和BCG-Em14-3-3疫苗免疫小鼠后IgG及其业类和IgE的变化.方法 12~14周龄、体质量20~25 g的雌性Balb/c小鼠40只,鼻腔内接种上述疫苗,在0、2、4、6、8、10、12、14、16和18周按体质量随机剖杀4只小鼠,经眼球取血,常规酶联免疫吸附试验法测定血清中IgG及其亚类和IgE水平.结果 Balb/c小鼠的血清IgG、IgG2a和IgG2b水平均在免疫后第2~18周升高,并分别在免疫后第10、4和4周达到

  4. 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.

  5. 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.

  6. 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...

  7. 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%.

  8. 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

  9. Expression of cellular components in granulomatous inflammatory response in Piaractus mesopotamicus model.

    Directory of Open Access Journals (Sweden)

    Wilson Gómez Manrique

    Full Text Available The present study aimed to describe and characterize the cellular components during the evolution of chronic granulomatous inflammation in the teleost fish pacus (P. mesopotamicus induced by Bacillus Calmette-Guerin (BCG, using S-100, iNOS and cytokeratin antibodies. 50 fish (120±5.0 g were anesthetized and 45 inoculated with 20 μL (40 mg/mL (2.0 x 10(6 CFU/mg and five inoculated with saline (0,65% into muscle tissue in the laterodorsal region. To evaluate the inflammatory process, nine fish inoculated with BCG and one control were sampled in five periods: 3rd, 7th, 14th, 21st and 33rd days post-inoculation (DPI. Immunohistochemical examination showed that the marking with anti-S-100 protein and anti-iNOS antibodies was weak, with a diffuse pattern, between the third and seventh DPI. From the 14th to the 33rd day, the marking became stronger and marked the cytoplasm of the macrophages. Positivity for cytokeratin was initially observed in the 14th DPI, and the stronger immunostaining in the 33rd day, period in which the epithelioid cells were more evident and the granuloma was fully formed. Also after the 14th day, a certain degree of cellular organization was observed, due to the arrangement of the macrophages around the inoculated material, with little evidence of edema. The arrangement of the macrophages around the inoculum, the fibroblasts, the lymphocytes and, in most cases, the presence of melanomacrophages formed the granuloma and kept the inoculum isolated in the 33rd DPI. The present study suggested that the granulomatous experimental model using teleost fish P. mesopotamicus presented a similar response to those observed in mammals, confirming its importance for studies of chronic inflammatory reaction.

  10. A survey of health professions students for knowledge, attitudes, and confidence about tuberculosis, 2005

    Directory of Open Access Journals (Sweden)

    Catanzaro Antonino

    2007-08-01

    Full Text Available Abstract Background In 2003 the NIH perceived a need to strengthen teaching about tuberculosis (TB to health professions students. The National Tuberculosis Curriculum Consortium (NTCC was funded to meet this need. The purpose of this study was to survey students enrolled in NTCC schools prior to NTCC-developed educational materials being made available to faculty. Methods A self-administered survey for students in NTCC schools to establish a baseline level of knowledge, attitudes, and confidence about tuberculosis. Results 1480/2965 (50% students in 28 programs in 20 NTCC schools completed the survey. If public health students are eliminated from totals (only 61 respondents of 765 public health students, the overall response proportion for the seven clinically-related disciplines was 64.5%. The majority (74% were in schools of medicine (MD/DO, undergraduate nursing (BSN, and pharmacy (PharmD; others were in programs for physician assistants (PA, advanced practice nursing (NP/APN, respiratory therapy (RT, clinical laboratory sciences (MT/CLS, and public health (MPH. Almost 90% had attended at least one lecture about TB. Although 91.4% knew TB was transmitted via aerosols, about one-third did not know the method for administering tuberculin, or that Bacillus Calmette-Guerin (BCG vaccine was not a contraindication to TB skin testing. Fewer than two-thirds knew that about 10% of people in the U.S.A. who have latent tuberculosis infection (LTBI and a normal immune system will develop TB disease, or that BCG is not part of the routine vaccination program in the U.S.A. because it complicates surveillance for new TB infection. Conclusion There is room for improvement in knowledge, attitudes, and confidence about TB by health professions students surveyed. The NTCC-developed educational products may be used by faculty to improve student performance to be assessed with future surveys.

  11. MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE IN EGYPTIAN CHILDREN

    Directory of Open Access Journals (Sweden)

    Nermeen Galal

    2012-05-01

    Full Text Available Background: Tuberculosis remains a major health problem in developing countries especially with the emergence of multidrug resistant strains. Mendelian Susceptibility to Mycobacterial Disease (MSMD is a rare disorder with impaired immunity against mycobacterial pathogens. Reported MSMD etiologies highlight the crucial role of the Interferon gamma /Interleukin 12 (IFN-g/ IL-12 axis and the phagocyte respiratory burst axis. Purpose: Screen patients with possible presentations for MSMD. Methods: Patients with disseminated BCG infection following vaccination, atypical mycobacterial infections or recurrent tuberculosis infections were recruited from the Primary Immune Deficiency Clinic at Cairo University Specialized Pediatric Hospital, Egypt and immune and genetic laboratory investigations were conducted at Human Genetic of Infectious Diseases laboratory in Necker Medical School, France from 2005-2009. IFN-g level in patient’s plasma as well as mutations in the eight previously identified MSMD-causing genes were explored. Results: Nine cases from eight (unrelated kindreds were evaluated in detail. We detected a high level of IFN-g in plasma in one patient. Through Sanger sequencing, a homozygous mutation in the IFNGR1 gene at position 485 corresponding to an amino acid change from serine to phenylalanine (S485F, was detected in this patient. Conclusion: We report the first identified cases of MSMD among Egyptian patients, including in particular a new IFNGR1 mutation underlying IFN-gR1 deficiency. The eight remaining patients need to be explored further. These findings have implications regarding the compulsory Bacillus Calmette Guerin vaccination policy in Egypt, especially given the high consanguinity rate. Keywords: Interferon gamma axis, mycobacterium tuberculosis, BCG, consanguinity

  12. MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE IN EGYPTIAN CHILDREN

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    Nermeen Galal

    2012-01-01

    Full Text Available

    Background: Tuberculosis remains a major health problem in developing countries especially with the emergence of multidrug resistant strains. Mendelian Susceptibility to Mycobacterial Disease (MSMD is a rare disorder with impaired immunity against mycobacterial pathogens. Reported MSMD etiologies highlight the crucial role of the Interferon gamma /Interleukin 12 (IFN-g/ IL-12 axis and the phagocyte respiratory burst axis.

    Purpose: Screen patients with possible presentations for MSMD.

    Methods: Patients with disseminated BCG infection following vaccination, atypical mycobacterial infections or recurrent tuberculosis infections were recruited from the Primary Immune Deficiency Clinic at Cairo University Specialized Pediatric Hospital, Egypt and immune and genetic laboratory investigations were conducted at Human Genetic of Infectious Diseases laboratory in Necker Medical School, France from 2005-2009. IFN-g level in patient’s plasma as well as mutations in the eight previously identified MSMD-causing genes were explored.

    Results: Nine cases from eight (unrelated kindreds were evaluated in detail. We detected a high level of IFN-g in plasma in one patient. Through Sanger sequencing, a homozygous mutation in the IFNGR1 gene at position 485 corresponding to an amino acid change from serine to phenylalanine (S485F, was detected in this patient.

    Conclusion: We report the first identified cases of MSMD among Egyptian patients, including in particular a new IFNGR1 mutation underlying IFN-gR1 deficiency. The eight remaining patients need to be explored further. These findings have implications regarding the compulsory Bacillus Calmette Guerin vaccination policy in Egypt, especially given the high consanguinity rate.

    Keywords: Interferon gamma axis, mycobacterium tuberculosis, BCG, consanguinity

  13. [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.

  14. 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.

  15. Comparative Ser/Thr/Tyr phosphoproteomics between two Mycobacterial species: The fast growing Mycobacterium smegmatis and the slow growing Mycobacterium bovis BCG.

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    Kehilwe Confidence Nakedi

    2015-04-01

    Full Text Available Ser/Thr/Tyr protein phosphorylation plays a critical role in regulating mycobacterial growth and development. Understanding the mechanistic link between protein phosphorylation signaling network and mycobacterial growth rate requires a global view of the phosphorylation events taking place at a given time under defined conditions. In the present study we employed a phosphopeptide enrichment and high throughput mass spectrometry-based strategy to investigate and qualitatively compare the phosphoproteome of two mycobacterial model organisms: the fast growing Mycobacterium smegmatis and the slow growing Mycobacterium bovis BCG. Cells were harvested during exponential phase and our analysis detected a total of 185 phospho-sites in M. smegmatis, of which 106 were confidently localized (localization probability (LP =0.75; PEP=0.01. By contrast, in M. bovis BCG the phosphoproteome comprised 442 phospho-sites, of which 289 were confidently localized. The percentage distribution of Ser/Thr/Tyr phosphorylation was 39.47, 57.02 and 3.51 % for M. smegmatis and 35, 61.6 and 3.1% for M. bovis BCG. Moreover, our study identified a number of conserved Ser/Thr phosphorylated sites and conserved Tyr phosphorylated sites across different mycobacterial species. Overall a qualitative comparison of the fast and slow growing mycobacteria suggests that the phosphoproteome of M. smegmatis is a simpler version of that of M. bovis BCG. In particular, M. bovis BCG exponential cells exhibited a much more complex and sophisticated protein phosphorylation network regulating important cellular cycle events such as cell wall biosynthesis, elongation, cell division including immediately response to stress. The differences in the two phosphoproteomes are discussed in light of different mycobacterial growth rates.

  16. Selection bias: neighbourhood controls and controls selected from those presenting to a Health Unit in a case control study of efficacy of BCG revaccination

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    de Souza Wayner V

    2007-02-01

    Full Text Available Abstract Background In most case control studies the hardest decision is the choice of the control group, as in the ideal control group the proportion exposed is the same as in the population that produced the cases. Methods A comparison of two control groups in a case control study of the efficacy of BCG revaccination. One group was selected from subjects presenting to the heath unit the case attended for routine prevention and care; the second group was selected from the neighbourhood of cases. All Health Units from which controls were selected offered BCG revaccination. Efficacy estimated in a randomized control trial of BCG revaccination was used to establish that the neighbourhood control group was the one that gave unbiased results. Results The proportion of controls with scars indicating BCG revaccination was higher among the control group selected from Health Unit attenders than among neighbourhood controls. This excess was not removed after control for social variables and history of exposure to tuberculosis, and appears to have resulted from the fact that people attending the Health Unit were more likely to have been revaccinated than neighbourhood controls, although we can not exclude an effect of other unmeasured variables. Conclusion In this study, controls selected from people presenting to a Health Unit overrepresented exposure to BCG revaccination. Had the results from the HU attenders control group been accepted this would have resulted in overestimation of vaccine efficacy. When the exposure of interest is offered in a health facility, selection of controls from attenders at the facility may result in over representation of exposure in controls and selection bias.

  17. HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

    Science.gov (United States)

    Jongwe, Tsungai Ivai; Chapman, Ros; Douglass, Nicola; Chetty, Shivan; Chege, Gerald; Williamson, Anna-Lise

    2016-01-01

    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). PMID:27427967

  18. HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

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    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.

  19. 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

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    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

  20. 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

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    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

  1. [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) PMID:7526022

  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. Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons

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    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.

  4. Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG Determining the risk of tuberculosis infection in BCG-vaccinated populations

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    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

  5. 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.

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

    Science.gov (United States)

    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.

  7. Induction of Unconventional T Cells by a Mutant Mycobacterium bovis BCG Strain Formulated in Cationic Liposomes Correlates with Protection against Mycobacterium tuberculosis Infections of Immunocompromised Mice.

    Science.gov (United States)

    Derrick, Steven C; Yabe, Idalia; Morris, Sheldon; Cowley, Siobhan

    2016-07-01

    Earlier studies aimed at defining protective immunity induced by Mycobacterium bovis BCG immunization have largely focused on the induction of antituberculosis CD4(+) and CD8(+) T cell responses. Here we describe a vaccine consisting of a BCGΔmmaA4 deletion mutant formulated in dimethyl dioctadecyl-ammonium bromide (DDA) with d-(+)-trehalose 6,6'-dibehenate (TDB) (DDA/TDB) adjuvant (A4/Adj) that protected TCRδ(-/-) mice depleted of CD4(+), CD8(+), and NK1.1(+) T cells against an aerosol challenge with M. tuberculosis These mice were significantly protected relative to mice immunized with a nonadjuvanted BCGΔmmaA4 (BCG-A4) mutant and nonvaccinated controls at 2 months and 9 months postvaccination. In the absence of all T cells following treatment with anti-Thy1.2 antibody, the immunized mice lost the ability to control the infection. These results indicate that an unconventional T cell population was mediating protection in the absence of CD4(+), CD8(+), NK1.1(+), and TCRγδ T cells and could exhibit memory. Focusing on CD4(-) CD8(-) double-negative (DN) T cells, we found that these cells accumulated in the lungs postchallenge significantly more in A4/Adj-immunized mice and induced significantly greater frequencies of pulmonary gamma interferon (IFN-γ)-producing cells than were seen in the nonvaccinated or nonadjuvanted BCG control groups. Moreover, pulmonary DN T cells from the A4/Adj group exhibited significantly higher IFN-γ integrated median fluorescence intensity (iMFI) values than were seen in the control groups. We also showed that enriched DN T cells from mice immunized with A4/Adj could control mycobacterial growth in vitro significantly better than naive whole-spleen cells. These results suggest that formulating BCG in DDA/TDB adjuvant confers superior protection in immunocompromised mice and likely involves the induction of long-lived memory DN T cells. PMID:27226281

  8. Enhanced superoxide release and tumoricidal activity by a postlavage, in situ pulmonary macrophage population in response to activation by Mycobacterium bovis BCG exposure.

    OpenAIRE

    Drath, D B

    1985-01-01

    The monocytic phagocyte population of rat lungs is heterogeneous. In addition to the freely lavagable alveolar macrophages, there is a fixed in situ tissue-associated subpopulation of pulmonary macrophages. The response of this subpopulation to classical macrophage activation by Mycobacterium bovis BCG exposure was monitored. Results indicate that this population can be activated both metabolically and functionally, as evidenced by enhanced release of superoxide anions and demonstrable tumori...

  9. 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.

  10. 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.

  11. 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

  12. Efficacy of intramuscular BCG polysaccharide nucleotide on mild to moderate bronchial asthma accompanied with allergic rhinitis: a randomized, double blind, placebo-controlled study

    Institute of Scientific and Technical Information of China (English)

    LI Jing; LUO Ding-fen; LI Sui-ying; SUN Bao-qing; ZHONG Nan-shan

    2005-01-01

    Background Atopy is a state of allergy to common antigens and is founded on an immune disturbance of exuberant Th2 activity and IgE production. There is also epidemiological and experimental evidence that exposure to mycobacteria has the potential to suppress the development of asthma or atopy. Since Th1 and Th2 immune mechanisms are significantly antagonistic, it is hypothesized that mycobacterial exposure may moderate atopic disease by modification of immune responses. Methods One hundred and twenty mild to moderate persistent asthmatics accompanied with allergic rhinitis were randomly divided into four groups with one injection every other day for 18 times for group A with 1 ml of normal saline, B with 0.5 mg of Bacillus Calmette-Guérin polysaccharide nucleotide (BCG-PSN) and C with 1 mg of BCG-PSN, 36 times for group D with 0.5 mg of BCG-PSN. Markers for the severity of asthma and rhinitis including the amount of inhaled corticosteriod, bronchodilator and oral H1 blocker-loratidine being used to obtain optimal symptomatic control, symptom scores of asthma and allergic rhinitis, peak expiratory flow (PEF), histamine provocative dose that produces at least a 20% change in forced expiratory volume with in 1 second (PD20-FEV1), blood IgE levels as well as dermatophagoides pteronysinus (DP) and dermatophagoides farinae (DF) skin prick test were measured every visit for 6 months. Results There were no differences for symptom scores of asthma, daily use of bronchodilator, PEF, PD20-FEV1, blood IgE as well as DF and DP skin prick test among the four groups. Score for allergic rhinitis decreased significantly in groups B, C and D on day 36 and 72 as compared with group A (P<0.05). Score for allergic rhinitis increased after day 72 in group B and C while it was significantly lower in group D (P<0.05). The patients in group D used less amount of inhaled beclomethosone than other groups (P<0.05) from day 72 after the treatment to day 180. Oral loratadine consumption in

  13. Characterization of immune response to killed leishmania major promastigotes plus BCG vaccine in Sudanese volunteers: a double-blind placebo controlled study

    International Nuclear Information System (INIS)

    This work was examined whether intradermal immunization of healthy adult Sudanese volunteers with killed leishmania major (KLM) promastigotes plus BCG would induce antigen-specific T cell responses. Only healthy Sudanese volunteers with negative reactivity to leishmania skin test and with ≤20 mm induration of reactivity to purified protein derivative (PPD) were included in the trial. Group (A) (n=3): received a single dose (0.1ml) at a concentration of 10 mg protein of a whole cell component of KLM promastigotes/ml BCG, group (B) (n=12): received as a single dose of viable attenuated BCG alone (0.1 ml) at a concentration of 1 mg protein/ml diluent, group (C) (n=11): received the vaccine diluent only (Placebo) (o.1 ml). Study subjects were tested for their immunological and clinical responses before intervention, . Following vaccination 65% of group (A) subjects converted in their reactivity to leishmanin skin testing,non of the BCG vaccinated subjects converted in leishmanin skin test and only one subject of group (C) became leishmanin positive. Levels of Interferon-gamma (IFN-γ), interleukin-5 (IL-5) and interleukin-10 (IL-10) were measured by a double sandwich enzyme-linked immunosorbent assay (ELISA). A vaccine was considered as a positive responder in terms of cytokine production when the level of the produced cytokine was equal to the 80th percentile of the levels produced by the volunteers in the placebo group. 92% of the group vaccinated with KLM=BCG had circulating T cells. No significant of IL-5 or Il-10 was reported in any of the volunteers in the three group. Levels of antileishmania specific IgG were measured by ELISA in optical densities. Volunteers with mean antibody titre above the cut-off point (mean=3X standard deviation) were considered to have positive scores. Accordingly after vaccination 7.69% one volunteers in group (A) had a positive antibody response corresponding to 0% in the other two groups. No serious side effects were reported

  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. Effect of media use on mothers' vaccination of their children in sub-Saharan Africa.

    Science.gov (United States)

    Jung, Minsoo; Lin, Leesa; Viswanath, Kasisomayajula

    2015-05-21

    While several studies have examined the crucial role that parents' vaccination behaviors play in reducing disease spread and severity among children, few have evaluated the connection between parents' media use and their decision on whether or not to vaccinate their child, specifically in relation to the BCG (Bacillus Calmetter Guerin), DPT (Diptheria, Pertussis, Tetanus) polio, and measles vaccines. Media channels are a critical source of health information for parents, which is especially true in Sub-Saharan Africa, as there is often a dearth of local healthcare providers. The aim of this paper is to investigate the role that media use plays in a mothers' choice to vaccinate their infant children in sub-Saharan Africa, specifically focusing on whether media use is associated with socioeconomic status (SES) and a mothers' vaccination of their children. Cross-sectional data from the Demographic Health Surveys of 13 sub-Saharan countries (2004-2010) were pooled. A multivariate Poisson regression of 151,209 women was used to calculate adjusted relative ratios and 95% confidence intervals for the associations among SES, media use, and immunization. Education and wealth were found to be strongly and positively associated with vaccine-uptake behaviors. The effects of media use (radio and television) were found to be associated with the relationships between SES and vaccine uptake. However, it did not reduce the impact of SES on vaccination. These findings indicate that mass media may be an important tool for future efforts to reduce the health discrepancies between children from high- and low-socioeconomic backgrounds. Going forward, immunization strategies should include communication plans that will address and mitigate potential immunization disparities among parents of different SES backgrounds. PMID:25896379

  16. A recombinant adenovirus expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis elicits strong antigen-specific immune responses in mice.

    Science.gov (United States)

    Li, Wu; Deng, Guangcun; Li, Min; Zeng, Jin; Zhao, Liping; Liu, Xiaoming; Wang, Yujiong

    2014-11-01

    Tuberculosis (TB) is caused by an infection of Mycobacterium tuberculosis (Mtb) and remains an enormous and increasing health burden worldwide. To date, Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the only licensed anti-TB vaccine worldwide, which provides an important but limited protection from the Mtb infection. The development of alternative anti-TB vaccines is therefore urgently needed. Here we report, the generation of Ad5-CEAB, a recombinant adenovirus expressing Mtb antigens of CFP10, ESAT6, Ag85A and Ag85B proteins in a form of mixture. In order to evaluate the immunogenicity of Ad5-CEAB, mice were immunized with Ad5-CEAB by intranasal instillation three times with 2-week intervals. The results demonstrated that Ad5-CEAB elicited a strong antigen-specific immune response, particularly of the Th1 immune responses that were characterized by an increased ratio of IgG2a/IgG1 and secretions of Th1 type cytokines, IFN-γ, TNF-α, IL-2 and IL-12. In addition, the Ad5-CEAB also showed an ability to enhance humoral responses with a dramatically augmented antigen-specific serum IgG. Furthermore, an elevated sIgA were also found in the bronchoalveolar lavage fluid of the immunized mice, suggesting the elicitation of mucosal immune responses. These data indicate that Ad5-CEAB can induce a broad range of antigen-specific immune responses in vivo, which provides a promising and novel route for developing anti-TB vaccines and warrants further investigation.

  17. Effect of media use on mothers' vaccination of their children in sub-Saharan Africa.

    Science.gov (United States)

    Jung, Minsoo; Lin, Leesa; Viswanath, Kasisomayajula

    2015-05-21

    While several studies have examined the crucial role that parents' vaccination behaviors play in reducing disease spread and severity among children, few have evaluated the connection between parents' media use and their decision on whether or not to vaccinate their child, specifically in relation to the BCG (Bacillus Calmetter Guerin), DPT (Diptheria, Pertussis, Tetanus) polio, and measles vaccines. Media channels are a critical source of health information for parents, which is especially true in Sub-Saharan Africa, as there is often a dearth of local healthcare providers. The aim of this paper is to investigate the role that media use plays in a mothers' choice to vaccinate their infant children in sub-Saharan Africa, specifically focusing on whether media use is associated with socioeconomic status (SES) and a mothers' vaccination of their children. Cross-sectional data from the Demographic Health Surveys of 13 sub-Saharan countries (2004-2010) were pooled. A multivariate Poisson regression of 151,209 women was used to calculate adjusted relative ratios and 95% confidence intervals for the associations among SES, media use, and immunization. Education and wealth were found to be strongly and positively associated with vaccine-uptake behaviors. The effects of media use (radio and television) were found to be associated with the relationships between SES and vaccine uptake. However, it did not reduce the impact of SES on vaccination. These findings indicate that mass media may be an important tool for future efforts to reduce the health discrepancies between children from high- and low-socioeconomic backgrounds. Going forward, immunization strategies should include communication plans that will address and mitigate potential immunization disparities among parents of different SES backgrounds.

  18. Uptake and accumulation of oxidized low-density lipoprotein during Mycobacterium tuberculosis infection in guinea pigs.

    Directory of Open Access Journals (Sweden)

    Gopinath S Palanisamy

    Full Text Available The typical host response to infection of humans and some animals by M. tuberculosis is the accumulation of reactive oxygen species generating inflammatory cells into discrete granulomas, which frequently develop central caseous necrosis. In previous studies we showed that infection of immunologically naïve guinea pigs with M. tuberculosis leads to localized and systemic oxidative stress that results in a significant depletion of serum total antioxidant capacity and the accumulation of malondialdehyde, a bi-product of lipid peroxidation. Here we show that in addition, the generation of excessive reactive oxygen species in vivo resulted in the accumulation of oxidized low density lipoproteins (OxLDL in pulmonary and extrapulmonary granulomas, serum and lung macrophages collected by bronchoalveolar lavage. Macrophages from immunologically naïve guinea pigs infected with M. tuberculosis also had increased surface expression of the type 1 scavenger receptors CD36 and LOX1, which facilitate the uptake of oxidized host macromolecules including OxLDL. Vaccination of guinea pigs with Bacillus Calmette Guerin (BCG prior to aerosol challenge reduced the bacterial burden as well as the intracellular accumulation of OxLDL and the expression of macrophage CD36 and LOX1. In vitro loading of guinea pig lung macrophages with OxLDL resulted in enhanced replication of bacilli compared to macrophages loaded with non-oxidized LDL. Overall, this study provides additional evidence of oxidative stress in M. tuberculosis infected guinea pigs and the potential role OxLDL laden macrophages have in supporting intracellular bacilli survival and persistence.

  19. [Monetary incentives for a more effective immunization program].

    Science.gov (United States)

    Zi, W

    1990-01-01

    In 1984 an insurance plan for child immunization was introduced in the counties of Wuji, Linzhang, an Zunhua, and in the city of Xingtai in the province of Hebei, China. The remuneration of village physicians and payment for vaccination services was linked to their effectiveness. In Wuji county children under 2 up to the age of 7 could be enrolled. If a child contracted measles, $8.50 was paid as compensation, $29 for tetanus, $43 for diphtheria, and $57 for poliomyelitis. If death was caused by one of these diseases, $85 was paid. 84% of children of this age range participated in the plan. 36% of the money from policy purchases of $36,000 was allocated to compensation and administration and 64% to municipal health centers for replacement of supplies and to village doctors performing vaccinations whose annual income ranged between $86 and $286 plus $37 for vaccinations. In the 1st year 31 cases were compensated for a total of $600. In the other countries similar schemes were operational: rural doctors pitched in with 5-20-25% of compensation, and the health care system paid the rest. In 1987, two-thirds of cities in the province adopted this plan enlisting 2,559,780 children (31% of those under 7) and accumulating a total fund of $2,500,000. A 1987 sample of 36, 992 children indicated a 94% coverage for BCG (bacillus Calmette-Guerin), 85% for poliomyelitis, 80% for DPT (diphtheria-pertussis-tetanus), 80% for measles, 90% for Japanese B encephalitis and epidemic meningitis. In 1986, there were 273,000 fewer cases of measles, polio, diphtheria, pertussis, epidemic meningitis, and Japanese encephalitis with 4200 fewer deaths, and 3000 fewer incapacities (or possibly 1,000,000, 15,000 and 5000 fewer, respectively, because of nonreporting). Measles morbidity declined from 16/100,000 in 1986 to 3.7/100,000 in the first 11 months of 1987.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 多房棘球绦虫Em14-3-3抗原编码基因在BCG中的表达%Expression of Echinococcus multilocularis 14-3-3 antigen encoding gene in BCG

    Institute of Scientific and Technical Information of China (English)

    王鸿; 李文桂

    2006-01-01

    目的:研究多房棘球绦虫Em14-3-3抗原编码基因在BCG中的表达.方法:将重组质粒pBCG-Em14-3-3用电穿孔法导人BCG构建rBCG,将含有重组子的细菌培养至对数生长期,在收菌前3天每天45℃热诱导30min,然后对表达产物作SDS-PAGE及免疫印迹分析.结果:多房棘球绦虫pBCG-Em14-3-3在BCG中成功表达了Em14-3-3重组蛋白,在相对分子量为27KDa处可见明显的表达蛋白带,其表达量占菌体总蛋白量的11%.结论:多房棘球绦虫pBCG-Emi4-3-3能在BCG中高效表达,且能与鼠血清抗体发生特异结合,提示rBCG-Em14-3-3疫苗表达的Em14-3-3重组蛋白具有特异的抗原性.

  2. 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.

  3. Co-administration of IL-1+IL-6+TNF-α with Mycobacterium tuberculosis infected macrophages vaccine induces better protective T cell memory than BCG.

    Directory of Open Access Journals (Sweden)

    Vijender Singh

    Full Text Available BCG has been administered globally for more than 75 years, yet tuberculosis (TB continues to kill more than 2 million people annually. Further, BCG protects childhood TB but is quite inefficient in adults. This indicates that BCG fails to induce long-term protection. Hence there is a need to explore alternative vaccination strategies that can stimulate enduring T cell memory response. Dendritic cell based vaccination has attained extensive popularity following their success in various malignancies. In our previous study, we have established a novel and unique vaccination strategy against Mycobacterium tuberculosis (M. tb and Salmonella typhimurium by utilizing infected macrophages (IM. In short-term experiments (30 days, substantial degree of protection was observed. However, remarkable difference was not observed in long-term studies (240 days due to failure of the vaccine to generate long-lasting memory T cells. Hence, in the present study we employed T cell memory augmenting cytokines IL-1+IL-6+TNF-α and IL-7+IL-15 for the induction of the enhancement of long-term protection by the vaccine. We co-administered the M. tb infected macrophages vaccine with IL-1+IL-6+TNF-α (IM-1.6.α and IL-7+IL-15 (IM-7.15. The mice were then rested for a reasonably large period (240 days to study the bona fide T cell memory response before exposing them to aerosolized M. tb. IM-1.6.α but not IM-7.15 significantly improved memory T cell response against M. tb, as evidenced by recall responses of memory T cells, expansion of both central as well as effector memory CD4 and CD8 T cell pools, elicitation of mainly Th1 memory response, reduction in the mycobacterial load and alleviated lung pathology. Importantly, the protection induced by IM-1.6.α was significantly better than BCG. Thus, this study demonstrates that not only antigen-pulsed DCs can be successfully employed as vaccines against cancer and infectious diseases but also macrophages infected with M. tb

  4. Analisis Matriks Boston Consulting Group (BCG untuk Memenangkan Strategi Organisasi (Studi Kasus Perguruan Tinggi Di Kopertis Wilayah III – DKI Jakarta

    Directory of Open Access Journals (Sweden)

    Haryadi Sarjono

    2013-05-01

    Full Text Available This research intends to know position of market growth in higher education, especially Sekolah Tinggi, based on market share, using BCG metrics. Unit analysis is all private higher educations in Kopertis III – DKI Jakarta, consisting of University, Sekolah Tinggi, Institute, and Academics. The object of analysis is the numberof new student admission. Method of data collection in this paper is field research including observation and literature research method. The secondary data used in this study is data from Kopertis region III. Based on the results of the study, it is obtained Sekolah Tinggi for the academic year 2008 and 2009 is in quadrant III (Cash Cow.

  5. Effects of BCG-CpG-DNA on signal transducers and activators 4,6 in asthmatic mice lung%BCG-CpG-DNA对支气管哮喘小鼠肺组织STAT4、STAT6表达的影响

    Institute of Scientific and Technical Information of China (English)

    罗珲; 徐湛; 孙大勇

    2015-01-01

    目的 观察BCG-CpG-DNA干预对支气管哮喘(简称哮喘)小鼠信号转导和转录激活因子4(STAT4)、STAT6的影响,探讨其对小鼠哮喘的作用机制.方法 将30只BALB/c小鼠随机分为3组:正常对照组(A组)、哮喘模型组(B组)、BCG-CpG-DNA治疗组(C组).其中B、C组小鼠于第0天、第13天分别给予卵清白蛋白(OVA)和佐剂液态铝混悬液致敏,于第25天至第30天每天给予雾化OVA建立哮喘模型,C组于致敏后以BCG-CpG-DNA腹腔注射,A组以生理盐水代替OVA致敏和激发.所有动物于第31天处死,采用Western blot技术检测小鼠肺组织中STAT4、STAT6的蛋白表达水平.结果 与A组比较,B组STAT4、pSTAT4表达降低(P值均<0.01),STAT6、pSTAT6的表达升高(P值均<0.01);与B组比较,BCG-CpG-DNA治疗后小鼠哮喘症状和肺组织的炎症病理变化减轻,STAT4、pSTAT4表达增加,STAT6、pSTAT6表达降低,差异具有统计学意义(P值均<0.01).结论 BCG-CpG-DNA可能通过抑制STAT6、促进STAT4的表达,调节Th1/Th2细胞因子平衡,从而起到抑制气道炎症的作用.%Objective To observe the influence of BCG-CpG-DNA on expression of signal transducers and activators of transcription 4 (STAT4),STAT6 in asthmatic mice lung,in order to discuss the potential mechanism of BCG-CpG-DNA in treating bronchial asthma (asthma).Methods Thirty BALB/c mice were randomly divided into three groups:normal control group (group A) and asthma model group (group B),BCG-CpG-DNA treated group (group C).Asthma model was established by OVA.Mice in group B and C were treated with mixed suspension of OVA and liquid aluminum adjuvant at day 0 and 13 respectively,and given aerosolized OVA from day 25 to 30,once every day.Mice in group C were intraperitoneal injected BCG-CpG-DNA after sensitization by OVA.OVA was replaced by physiological saline in group A.All the animals were killed at day 31.Western blot was performed to detect the protein expression level of STAT4 and STAT6 in

  6. Exosomes derived from M. Bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo.

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    Pramod K Giri

    Full Text Available Activation of both CD4(+ and CD8(+ T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma. Our previous studies showed that infected macrophages release from cells small membrane-bound vesicles called exosomes which contain mycobacterial lipid components and showed that these exosomes could stimulate a pro-inflammatory response in naïve macrophages. In the present study we demonstrate that exosomes stimulate both CD4(+ and CD8(+ splenic T cells isolated from mycobacteria-sensitized mice. Although the exosomes contain MHC I and II as well as costimulatory molecules, maximum stimulation of T cells required prior incubation of exosomes with antigen presenting cells. Exosomes isolated from M. bovis and M. tuberculosis infected macrophages also stimulated activation and maturation of mouse bone marrow-derived dendritic cells. Interestingly, intranasal administration of mice with exosomes isolated from M. bovis BCG infected macrophages induce the generation of memory CD4(+ and CD8(+ T cells. The isolated T cells also produced IFN-gamma upon restimulation with BCG antigens. The release of exosomes from infected macrophages may overcome some of the defects in antigen presentation associated with mycobacterial infections and we suggest that exosomes may be a promising M. tuberculosis vaccine candidate.

  7. The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Rodrigues, Amabelia; Yazdanbakhsh, Maria;

    2009-01-01

    Unexpectedly, we found no overall beneficial effect on mortality in a randomised trial of vitamin A supplementation (VAS) or placebo administered with BCG vaccine at birth in Guinea-Bissau. We conducted an explorative analysis to examine whether subsequent diphtheria-tetanus-pertussis (DTP......) vaccinations had modified the effect of VAS at birth. VAS was associated with a weak tendency for decreased mortality as long as BCG was the most recent vaccination, the mortality rate ratio being 0.86 (0.48-1.54); 0.82 (0.32-2.08) in girls and 0.89 (0.43-1.88) in boys. However, after DTP vaccination VAS...... at birth was associated with increased mortality in girls (2.19 (1.09-4.38)), whereas no difference was seen for boys (0.90 (0.44-1.82)) (p=0.08 for equal effect of VAS in the two sexes if DTP is the last vaccine). The explanation for the lack of beneficial effect in our setting may have been that VAS...

  8. Effects of maternal and infant co-infections, and of maternal immunisation, on the infant response to BCG and tetanus immunisation.

    Science.gov (United States)

    Elliott, Alison M; Mawa, Patrice A; Webb, Emily L; Nampijja, Margaret; Lyadda, Nancy; Bukusuba, Joseph; Kizza, Moses; Namujju, Proscovia B; Nabulime, Juliet; Ndibazza, Juliet; Muwanga, Moses; Whitworth, James A G

    2010-12-16

    Some vaccines show poor efficacy in tropical countries. Within a birth cohort in Uganda, we investigated factors that might influence responses to BCG and tetanus immunisation. Whole blood assay responses to crude culture filtrate proteins of Mycobacterium tuberculosis (cCFP)) and tetanus toxoid (TT) were examined among 1506 and 1433 one-year-olds, respectively. Maternal Mansonella perstans infection was associated with higher interleukin (IL)-10 responses to both immunogens but no reduction in gamma interferon (IFN-γ), IL-5 and IL-13 responses; other maternal helminth infections showed little effect. Tetanus immunisation during pregnancy was associated with higher infant responses to TT; maternal BCG scar (from past immunisation) with lower infant IL-5 and IL-13 responses to cCFP. IFN-γ, IL-5 and IL-13 to TT were reduced in HIV-exposed-uninfected infants; infant malaria and HIV were associated with lower IFN-γ, IL-5 and IL-13 responses to both immunogens. We conclude that maternal helminth infections are unlikely to explain poor vaccine efficacy in the tropics. Effects of maternal immunisation on infant responses to vaccines should be explored. Prevention of infant malaria and HIV could contribute to effectiveness of immunisation programmes. PMID:21040693

  9. Sex-differential and non-specific effects of routine vaccinations in a rural area with low vaccination coverage

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: We examined the potential sex-differential and non-specific effects of bacille Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP) and measles vaccine (MV) in a rural area of Senegal. METHODS: The 4133 children born in the area between 1996 and 1999 were included in the study....... Vaccinations were provided at three health centres. Vaccine information was collected through 3-monthly home visits. The survival analysis compared the effects of BCG and DTP according to the following sequence of vaccinations: BCG-first, BCG+DTP1-first, or DTP1-first. We compared DTP and MV between 9 and 24...

  10. ANALYSIS OF THE QUALITY OF NEONATAL BCG VACCINATION FROM 2006 TO 2009 IN SUZHOU%苏州市2006~2009年新生儿卡介苗接种质量分析

    Institute of Scientific and Technical Information of China (English)

    黄桥梁; 穆卫明; 颜建荣; 吴美芳; 孙明丽

    2012-01-01

    [Objective] To evaluate the completion and the effectiveness of BCC vaccination in Suzhou city during the year of 2006 to 2009, and analyze and resolve the problem in BCG vaccination, so as to.provide scientific evidence for tuberculosis control. [Methods] We conduct a analysis on BCG revaecination between Suzhou Center For Disease Prevention and Control and the effectiveness of BCG vaccination in the hospital of the district area in Suzhou, and compared with the PPD positive rate after 12 weeks' BCG vaccination among them. [Results] There were significant difference in BCG vaccination among the CDC and hospitals {P 0.05) in the PPD positive rate after 12 weeks' BCG vaccination. [Conclusion] It should improve the indications of BCG vaccination rate on the hospital in Suzhou, find out the potential tuberculosis as soon as possible, and avoid the newly infection.%[目的]了解苏州市2006~2009年新生儿卡介苗接种效果,为预时结核病提供科学依据.[方法]对在2006~2009年间市辖区医院出生时接种卡介苗和市疾控门诊补种卡介苗新生儿,进行结核菌素实验(PPD)观察比较.[结果]卡介苗接种市辖区医院、市疾控以及两者之间差异均有统计学意义(P<0.05);而在按种卡介苗3个月后PPD测试结果,市疾控与市辖区医院之间差异无统计学意义(P>0.05).[结论]进一步提高医院接种率水平,尽早发现患结核可能性患者,避免产生新的感染者.

  11. Revacinação BCG em escolares: evolução da lesão vacinal entre 48 horas e 10 semanas

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    Ferreira Arlan A.

    2002-01-01

    Full Text Available Objetivo: a reação cutânea na revacinação BCG tem sido motivo de questionamentos dado à sua magnitude. Seria ela intensa o suficiente para desencorajar seu uso na idade escolar? O objetivo deste estudo é descrever o aspecto evolutivo da lesão vacinal entre 48 horas e a décima semana pós-revacinação. Métodos: estudo de coorte descritivo em que foram revacinadas 484 crianças entre seis e 11 anos de idade, com 0,1ml da vacina BCG Moreau, e aferidos eritema, enduração, pústula, úlcera, crosta e cicatriz em 48h, 72h e, semanalmente, até a décima semana de evolução, acompanhadas no período de julho a dezembro de 1997. Os dados foram informatizados em programa Epi-Info 6.0, avaliando-se freqüências, médias, medianas e desvios-padrões. Resultados: enduração estava presente em 99,1%, e eritema em 91,6% das 438 crianças avaliadas com 48h. Pústulas foram observadas na primeira semana em 26,1% de 479 crianças. Na segunda semana, já apareceram as primeiras úlceras. Na décima semana, 69,8% das 463 crianças presentes exibiam crostas, mas apenas 29,2% havia completado o processo de cicatrização. Conclusão: a revacinação BCG em escolares produz intensa e precoce reação, que pode ser atribuível ao fenômeno de Koch, mas sem a esperada redução no tempo de cicatrização. Se por um lado a magnitude da reação não chega a comprometer sua indicação na idade escolar, a pronta resposta inflamatória aponta para a ativa resposta imune possivelmente remanescente da primo-vacinação.

  12. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

  13. The Effect of 50 000 IU Vitamin A with BCG Vaccine at Birth on Growth in the First Year of Life

    DEFF Research Database (Denmark)

    Fisker, Ane Bærent; Benn, Christine Stabell; Diness, Birgitte Rode;

    2011-01-01

    Vitamin A supplements may interact with diphtheria-tetanus-pertussis (DTP) vaccine causing increased female mortality. In a randomised trial of neonatal vitamin A supplementation (VAS), we examined growth during the first year of life in 808 children, pursuing the hypothesis that a negative...... interaction between VAS and DTP in girls would be reflected in growth. Length and weight were measured at 6 weekly visits and WHO-growth-reference z-scores derived. Neonatal VAS had no effect on anthropometric measures at 12 months, but may interact sex differentially with routine vaccines. While BCG...... was the most recent vaccine, neonatal VAS benefitted growth (difference in weight-for-length z-score (dWFL: 0.31(95% CI: 0.03-0.59)). While DTP was the most recent vaccine, VAS tended to affect growth adversely in girls (dWFL = -0.21 (-0.48-0.06)). After measles vaccine (MV) there was no overall effect...

  14. Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age

    DEFF Research Database (Denmark)

    Fisker, Ane B; Lisse, Ida M; Aaby, Peter;

    2007-01-01

    with higher (9%; 95% CI: 2, 17%) RBP concentrations in children of noneducated mothers but not in children of educated mothers. Overall, RBP concentrations increased between 6 wk and 4 mo of age. The increase correlated inversely with the number of diphtheria-tetanus-pertussis (DTP) vaccines received......BACKGROUND: The effect of vitamin A supplementation (VAS) at birth on subsequent vitamin A status has not been studied. OBJECTIVE: The objective was to study the effect of 50,000 IU vitamin A administered with BCG vaccine at birth on vitamin A status in both sexes. DESIGN: Within a randomized...... A recipients, subsequent DTP vaccines affected vitamin A status negatively. The main trial was registered at clinicaltrials.gov as NCT00168597....

  15. Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age

    DEFF Research Database (Denmark)

    Fisker, Ane B; Lisse, Ida M; Aaby, Peter;

    2007-01-01

    with higher (9%; 95% CI: 2, 17%) RBP concentrations in children of noneducated mothers but not in children of educated mothers. Overall, RBP concentrations increased between 6 wk and 4 mo of age. The increase correlated inversely with the number of diphtheria-tetanus-pertussis (DTP) vaccines received......BACKGROUND: The effect of vitamin A supplementation (VAS) at birth on subsequent vitamin A status has not been studied. OBJECTIVE: The objective was to study the effect of 50,000 IU vitamin A administered with BCG vaccine at birth on vitamin A status in both sexes. DESIGN: Within a randomized...... A recipients, subsequent DTP vaccines affected vitamin A status negatively. The main trial was registered at clinicaltrials.gov as NCT00168597. Udgivelsesdato: 2007-Oct...

  16. Vaccines Through Centuries: Major Cornerstones of Global Health.

    Science.gov (United States)

    Hajj Hussein, Inaya; Chams, Nour; Chams, Sana; El Sayegh, Skye; Badran, Reina; Raad, Mohamad; Gerges-Geagea, Alice; Leone, Angelo; Jurjus, Abdo

    2015-01-01

    Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the "Germ Theory of disease" of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette-Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, "The Decade of vaccines" was launched, and on April 1st 2012, the United Nations launched the "shot@Life" campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines

  17. Pharmaceutical characterization of Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine used for the treatment of superficial bladder cancer.

    Science.gov (United States)

    Groves, M J

    1993-06-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine, developed in the 1920s as a treatment and prophylactic for tuberculosis, has proved to be a nonspecific stimulant of the immune system and is now the major form of clinical immunotherapy approved for the treatment of superficial bladder cancer in the United States. However, methods for the production and physical characterization of the vaccine have not been significantly developed since Calmette and Guérin first devised their process for attenuating the organism in 1908. When reconstituted with sterile water immediately before use, the vaccine consists of a suspension of cellular fragments and aggregates and a mixture of dead and living cells. The dose is determined by the number of colony-forming units that develop when the vaccine is allowed to grow in a nutrient medium. This measurement of dose and viability is misleading because each cellular aggregate may consist of several hundred individual cells, but only one need be living to give rise to a single visible colony. Viability should therefore be measured on the basis of residual ATP levels. In this report, the mode of action of BCG vaccine against bladder cancer is reviewed, and attention is drawn to some factors that may need to be controlled during manufacturing and subsequent quality assurance procedures. The morphology of the various parts of the complex pleomorphic life cycle of this Mycobacterium species has been investigated, and the vaccine has been physically evaluated to provide a characterization by contemporary methodologies, including measurement of ATP content and particle size distribution of the dispersed mycobacterial aggregates. PMID:8331524

  18. 多房棘球绦虫重组BCG-EmⅡ/3疫苗免疫小鼠后脾细胞亚群的动态观察%Subsets of splenocytes in mice immunized with recombinant BCG-EmⅡ/3 vaccine of Echinococcus multilocularis

    Institute of Scientific and Technical Information of China (English)

    李文桂; 朱佑明; 王鸿

    2008-01-01

    目的 动态观察多房棘球绦虫重组BCG-EmⅡ/3疫苗免疫小鼠后脾细胞亚群的变化.方法 将疫苗采用鼻腔内接种免疫Balb/c鼠,在免疫后0、2、4、6、8、10、12、14、16周和18周各剖杀4只小鼠取脾,分离脾细胞,流式细胞仪检测脾CD4+和CD8+T淋巴细胞亚群的百分比,同时设有PBS对照.结果 疫苗接种组的脾CD4+和CD8+ T细胞亚群分别在免疫后2~10周和2~18周升高,分别在免疫后4周和10周达最高水平.结论 多房棘球绦虫重组BCG-EmⅡ/3疫苗可诱导小鼠脾CD4+和CD8+T细胞亚群的增殖.

  19. Tuberculous meningitis in children: a review of clinical, laboratory, epidemiological, and therapeutic aspects and of the usefulness of BCG vaccination Meningitis tuberculosa en niños: una revisión de aspectos clínicos, de laboratorio, epidemiológicos y terapéuticos y de la utilidad de la vacunación con BCG

    Directory of Open Access Journals (Sweden)

    José William Cornejo Ochoa

    2010-08-01

    Full Text Available

    Tuberculous meningitis is the most frequent extrapulmonary form of tuberculosis in underdeveloped countries, among them Colombia. It is associated with high rates of morbidity and mortality. In this article a review is presented of the following aspects of the disease: clinical, epidemiological, therapeutic, prophylactic by means of BCG vaccination, laboratory diagnosis, and tomographic findings.

    La tuberculosis meníngea (MTB es la enfermedad tuberculosa extrapulmonar más frecuente en los países del tercer mundo, incluida Colombia, y tiene tasas altas de morbilidad y mortalidad. En este artículo se presenta una revisión de la literatura sobre los siguientes aspectos de la enfermedad: clínicos, epidemiológicos, de laboratorio, tomográficos, terapéuticos y de prevención con la vacuna BCG.

  20. Vaccination of national expanded program of immunization among children in Dalian city%大连市适龄儿童国家免疫规划疫苗接种情况调查

    Institute of Scientific and Technical Information of China (English)

    邹积丰; 贾秀岩; 王稳

    2012-01-01

    目的 了解辽宁省大连市儿童基础免疫接种现状,为制定免疫预防策略提供科学依据.方法 采用2阶段按容量比例概率抽样( PPS)方法,在全市11个区市县抽查210名2006-2007年出生儿童,进行卡介苗(BCG)、口服脊髓灰质炎减毒活疫苗(OPV)、百白破联合疫苗(DPT)、麻疹减毒活疫苗(MV)、乙型肝炎疫苗( HepB)接种情况免疫调查.结果 大连市适龄儿童建卡率为99.05%,建证率为97.14%,各种疫苗合格接种率分别为BCG 98.57%、OPV 98.57%、DPT98.10%、MV 95.24%、HepB 94.76%,HepB首针及时接种率为94.29%,五苗全程合格接种率为97.62%,卡痕率为96.67%.结论 大连市适龄儿童BCG、OPV、DPT、MV、HBV接种率均超过或接近95%,保持在较高水平.%Objective To examine the vaccination status of national expanded program of immunization (EPI) among children in Dalian city and to provide basis for making vaccinaion strategy. Methods Totally 210 children born between January 1,2006 to December 31,2007 were selected with probability proportional to size sampling and surveyed for vaccination status. Results The percentages of the children with vaccination record card and certificate were 99. 05% and 97. 14%. The ratio of the children with the full course of 5 vaccines vaccination ( Bacillus Calmette Guerin, oral poliomylitis live atteuated vaccine, diphtheria, tetanus, pertussis combined vaccine, mealses live attenuated vaccine, and hepatitis B vaccine) was form 94. 29% to 98. 57% . Over 90 percent of the children were immunized with first hepatitis B vaccine in time. Conclusion The results indicate that the vaccination status of the children in Dalian city is good.

  1. Maternal infection with Trypanosoma cruzi and congenital Chagas disease induce a trend to a type 1 polarization of infant immune responses to vaccines.

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    Nicolas Dauby

    Full Text Available BACKGROUND: We previously showed that newborns congenitally infected with Trypanosoma cruzi (M+B+ display a strong type 1 parasite-specific T cell immune response, whereas uninfected newborns from T. cruzi-infected mothers (M+B- are prone to produce higher levels of proinflammatory cytokines than control neonates (M-B-. The purpose of the present study was to determine if such fetal/neonatal immunological environments could alter the response to standard vaccines administered in early life. METHODOLOGY: Infants (6-7 months old living in Bolivia, an area highly endemic for T. cruzi infection, and having received Bacillus Calmette Guerin (BCG, hepatitis B virus (HBV, diphtheria and tetanus vaccines, were enrolled into the M+B+, M+B-, M-B- groups mentioned above. The production of IFN-gamma and IL-13, as markers of Th1 and Th2 responses respectively, by peripherical blood mononuclear cells stimulated with tuberculin purified protein derivative of Mycobacterium tuberculosis (PPD or the vaccinal antigens HBs, diphtheria toxoid (DT or tetanus toxoid (TT, as well as circulating levels of IgG antibodies against HBsAg, DT and TT were analyzed in infants. Cellular responses to the superantigen SEB were also monitored in M+B+, M+B-, M-B-infants and newborns. PRINCIPAL FINDINGS: M+B+ infants developed a stronger IFN-gamma response to hepatitis B, diphtheria and tetanus vaccines than did M+B- and M-B- groups. They also displayed an enhanced antibody production to HBsAg. This was associated with a type 1-biased immune environment at birth, since cells of M+B+ newborns produced higher IFN-gamma levels in response to SEB. M+B- infants produced more IFN-gamma in response to PPD than the other groups. IL-13 production remained low and similar in all the three groups, whatever the subject's ages or vaccine status. CONCLUSION: These results show that: i both maternal infection with T. cruzi and congenital Chagas disease do not interfere with responses to BCG

  2. The preliminary result of a prospective study of bladder conserving treatment using transurethral resection, transarterial chemotherapy and local involved field radiotherapy in invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nagano, Hisato; Nagata, Maki; Yamaguchi, Yoshio; Nagashima, Toshiyuki; Tanohata, Kazunori [Yokohama Rosai Hospital (Japan)

    2002-12-01

    Radical cystectomy has been a standard treatment for invasive urinary bladder cancer, however preservation therapy is being considered in many facilities as a clinical examination. After transurethral resection of the bladder (TUR-Bt), three-time transarterial infusion (TAI) of cisplatin (CDDP) 45 mg/m{sup 2}, methotrexate (MTX) 30 mg/m{sup 2} and local five-port external beam radiation therapy (EBRT) of 60 Gy/30 fx/ 6 wks were delivered concurrently. Because such reports of organ sparing treatment using TAI are few, a mono-arm prospective study was designed to evaluate the rate of complete response (CR) (Response Evaluation Criteria In Solid Tumor (RECIST) standard) and the incidence of acute toxicity (National Cancer Institute (NCI) standard) compared with previous reports in which intravenous chemotherapy was used in a tri-modality treatment protocol. Twenty-three patients with T{sub 2-4}N{sub 0}M{sub 0} or High risk T{sub 1}N{sub 0}M{sub 0} were registered (T{sub 1}; 7, T{sub 2}; 7, T{sub 3}; 8, T{sub 4}; 1). They were all in good performance status (PS) (0-1). CR rate after intravesical therapy with bacilli Calmette-Guerin (BCG) was eighty-seven percent (confidence interval (CI) 66-97%). There was a significant difference (p=0.03) between this value and that (CR rate=62%, n=299) calculated from two reports in which transvenous chemotherapy was used as one of the treatment modalities. Grade three white blood cell decrease was seen in twenty-six percent of patients. This was significantly higher than the value estimated from reports using cisplatin only as the single chemotherapy agent. An acute reaction of the urinary bladder and rectum was negligible. After fifteen-month follow-up, four patients relapsed and two showed metastatic lesions. According to the protocol, three of the former four had already received cystectomy, but one had undergone an intra-vesicle BCG injection because it showed non-invasive papillary histology, and reached CR again. M

  3. Investigación sobre epidemiología convencional y molecular de tuberculosis en Orizaba, Veracruz, 1995-2008 Research on conventional and molecular epidemiology of tuberculosis in Orizaba, Veracruz, 1995-2008

    Directory of Open Access Journals (Sweden)

    Ma Eugenia Jiménez-Corona

    2009-01-01

    Full Text Available Se describen los resultados de investigación del Consorcio Mexicano contra la Tuberculosis, en la Jurisdicción Sanitaria de Orizaba, Veracruz, entre 1995 y 2008. Las aportaciones principales de los trabajos se refieren a los siguientes rubros: 1. Epidemiología convencional y molecular (medición de la carga de la enfermedad, tendencias, factores de riesgo y grupos vulnerables; descripción de las consecuencias de la farmacorresistencia e identificación de factores que favorecen la transmisión en la comunidad y en los hospitales. 2. Desarrollo de técnicas rápidas para conservación de muestras respiratorias que permitan el aislamiento y diagnóstico de farmacorresistencia de M. tuberculosis en campo. 3. Evaluación de la prueba tuberculínica, respuesta inmunológica al Bacilo de Calmette-Guerin (BCG, biomarcadores de la respuesta inmunitaria y medidas de control. 4. Comentarios en torno a aspectos éticos de la investigación en tuberculosis. Además se describe el impacto en políticas públicas, la transferencia de tecnología, la formación de recursos humanos y las perspectivas a futuro.This study describes the achievements of the Mexican Consortium against Tuberculosis, in the Sanitary District of Orizaba, Veracruz, Mexico between 1995 and 2008. In brief, the main results can be classified as follows: 1 Conventional and molecular epidemiology (measurement of burden of disease, trends, risk factors and vulnerable groups, consequences of drug resistance, identification of factors that favor nosocomial and community transmission; 2 Development of diagnostic techniques to detect drug resistance, description of circulating clones and adaptation of simple techniques to be used in the field; 3 Evaluation of usefulness of tuberculin skin test, immunologic responses to BCG, impact of directly observed therapy for tuberculosis (DOTS, and study of immunological biomarkers and 4 Comments on ethical aspects of tuberculosis research. Additionally

  4. Observation on the Treatment Effect of Chronic Urticaria with BCG-polysaccharide Nucleic Acid Injection%卡介菌多糖核酸注射液治疗慢性荨麻疹疗效观察

    Institute of Scientific and Technical Information of China (English)

    马跃民

    2000-01-01

    目的:观察卡介菌多糖核酸注射液治疗慢性荨麻疹的疗效。方法:将门诊慢性荨麻疹患者85例分为对照组40例(男23例,女17例),给抗组胺药物及外用止痒剂等常规治疗。治疗组45例(男26例,女19例),在给抗组胺药物及外用止痒剂等常规治疗基础上加用卡介菌多糖核酸注射液。结果:治疗组有效率93.3%,对照组有效率72.5%,无副作用。结论:用卡介菌多糖核酸注射液治疗慢性荨麻疹有效、安全。%Objective: To investigate the effect of BCG-polysaccharide nucleic acid injection (BCG-PSN)on chronic urticaria. Methods: 85 cases of chronic urticaria were treated at the outpatient department. Among them 40Patients(male 23, female 17)were chosen as control. They were given routine treatment shch as antihistamine drugs and topical agents. The othet 45 patients (male 26, female 19)were included in the treatment group. In addition to the routine treatment, they received intramuscular injection of BCG-PSN. ResuIts:Toal cure rate was 93.3% in the treatment group and 72.5% in the control group. No adverse effect was observed. ConcIusion: BCG-PSN was both safe and effective in treating chronic urticaria.

  5. Effect Analysis of BCG Vaccination among Children in Hangu District of Tianjin%天津市汉沽区儿童卡介苗免疫接种效果分析

    Institute of Scientific and Technical Information of China (English)

    窦俊娟

    2011-01-01

    [Objective]To learn the immune effect of BCC vaccination among children in Hangu district of Tianjin in the past 3 years. [Methods]The PPD test results of 4281 children who have received the initial BCG vaccination were analyzed. [Results]The positive rates of PPD test of children aged 3~36 months old, 4 -5 years old and 6 ~7 years old in 2008, 2009 and 2010 were 97. 3% - 85.7% , 97.1 % ~ 83.3% and 97.2% ~90.0% respectively. [ Conclusion] The immune effect and vaccination quality of BCG vaccination among children in Hangu district of Tianjin is good in the past 3 years. The key to success of BCG vaccination is the quality of initial BCG vaccination in newboms.%目的 了解天津市汉沽辖区近3年内结核菌素儿童卡介苗接种的免疫效果.方法 对4 281名已初种卡介苗儿童结核菌素( PPD)试验结果进行分析.结果 3个月~3岁、4~5岁和6~7岁3个年龄组PPD试验阳性率,2008、2009和2010年分析为97.3%~85.7%、97.1% ~83.3%和97.2%~90.0%.结论汉沽近3年儿童卡介苗接种免疫效果较好,接种质量较高.抓好新生儿卡介苗初种质量,是提高卡介苗接种成功率的关键.

  6. 基于波士顿矩阵法的医疗设备安全模型的建立%Research on the building of the medical equipment safety model based on BCG Matrix

    Institute of Scientific and Technical Information of China (English)

    樊廷玖; 王维红; 李婷; 周晓辉

    2013-01-01

    目的:全面、客观和真实地对在用医疗设备安全做出整体评价,从中找出设备安全管理方面的薄弱环节,为医疗设备的科学管理提供合理化方案。方法:对设备安全性指标分解、优化,从安全性和重要性两方面进行量化处理,利用波士顿矩阵(BCG Matrix)法建立设备的安全模型,对其分析并找出薄弱环节,加以重点关注与整改。结果:建立医疗设备的安全模型,能够较为客观、真实地反映在用医疗设备阶段性安全状况。结论:利用BCG Matrix法建立的医疗设备安全模型,可以用于对医疗设备安全性的量化分析。%Objective: To provide reasonable proposals for hospital administration, one whole evaluation was made in comprehensively, objectively and truthfully on the medical equipment. Methods:To optimize safety indexes of the medical equipment, the safety model was build using BCG Matrix, analyse it and find out weak link to focus on and rehabilitation it. Results: The safety of the medical equipment can be reflected in comprehensively and truthfully by means of building its safety model. Conclusion:The safety model of using BCG Matrix can be quantize and analyze the safety of the medical equipment.

  7. Transcription analysis of the dnaA gene and oriC region of the chromosome of Mycobacterium smegmatis and Mycobacterium bovis BCG, and its regulation by the DnaA protein.

    Science.gov (United States)

    Salazar, Leiria; Guerrero, Elba; Casart, Yveth; Turcios, Lilia; Bartoli, Fulvia

    2003-03-01

    The regions flanking the Mycobacterium dnaA gene have extensive sequence conservation, and comprise various DnaA boxes. Comparative analysis of the dnaA promoter and oriC region from several mycobacterial species revealed that the localization, spacing and orientation of the DnaA boxes are conserved. Detailed transcriptional analysis in M. smegmatis and M. bovis BCG shows that the dnaN gene of both species and the dnaA gene of M. bovis BCG are transcribed from two promoters, whereas the dnaA gene of M. smegmatis is transcribed from a single promoter. RT-PCR with total RNA showed that dnaA and dnaN were expressed in both species at all growth stages. Analysis of the promoter activity using dnaA-gfp fusion plasmids and DnaA expression plasmids indicates that the dnaA gene is autoregulated, although the degree of transcriptional autorepression was moderate. Transcription was also detected in the vicinity of oriC of M. bovis BCG, but not of M. smegmatis. These results suggest that a more complex transcriptional mechanism may be involved in the slow-growing mycobacteria, which regulates the expression of dnaA and initiation of chromosomal DNA replication.

  8. Tyk2信号传导在表达OVA的重组卡介菌(rBCG-OVA)所致慢性胞内细菌感染小鼠模型的CD8+Tc1反应中的作用%Tyk2 signaling plays a critical role in the development of T cytotoxic 1 responses following chronic rBCG-OVA infections in mice

    Institute of Scientific and Technical Information of China (English)

    李伟

    2011-01-01

    Objective To elucidate potential roles of tyrosine kinase 2 (Tyk2) in the generation and maintenance of Ag-specific CD8+ T cells. Methods We followed the fate of OVA-specific CD8 + T cells in Tyk2-deficient ( Tyk2 -/- ) mice after infection with recombinant OVA-expressing BCG ( rBCGOVA ). Because the immunostimulatory BCG-derived peptides recognized by CD8 + T cells have not been defined, and the OVA is definite peptide for specific CD8 + T cells that has been accepted widely, therefore we examine the kinetics of the OVA-Ag-specific CD8 + T cell response after rBCG-OVA infection in mice.Tyk2-/- and wild type(Tyk2+/+ ) mice were inoculated with rBCG-OVA by intra-trachea( i. t. ), after the examination of bacterial growth in the lung and spleen, the population of CD8 + T cells were detected by FACS analysis, the epitope-specific CD8 + T cells were followed with tetrameric H-2Kb molecule folding with OVA257 264 peptide, and the kinetics of Ag-specific CD8 + Tc1 cells were detected by intracellular IFN-γ production in response to OVA257-264 peptide by cytokine FACS analysis. Results After rBCG-OVA challenge,the bacteria number in spleen and lung of Tyk2 -/- mice were significantly larger than those in Tyk2 +/+ mice on days 14, 21 and 49. Almost as same as that in Tyk2+/+ mice, the size of epitope-specific CD8+ T cella with OVA257-264/Kb-tetramer-positive and the CD8 +Tc1 (T eytotoxic 1 )cells positive for intracellular IFN-γ could proliferate to its peak on day 21, then contract and maintain to the memory phase in spleen and lung of Tyk2-/- mice, but the population of CD8+ T cells in spleen and lung of Tyk2 -/- mice were significantly smaller than those in Tyk2+/+ mice on days 21 and 49, the number of epitope-specific CD8+ T cells in spleen and lung of Tyk2 -/- mice were significantly decreased and the frequency of CD8 + Tc1 cells in spleen and lung of Tyk2 -/- mice significantly reduced on day 21,49 and 70 after rBCG-OVA infection. So correspond with the larger

  9. Enhanced superoxide release and tumoricidal activity by a postlavage, in situ pulmonary macrophage population in response to activation by Mycobacterium bovis BCG exposure.

    Science.gov (United States)

    Drath, D B

    1985-07-01

    The monocytic phagocyte population of rat lungs is heterogeneous. In addition to the freely lavagable alveolar macrophages, there is a fixed in situ tissue-associated subpopulation of pulmonary macrophages. The response of this subpopulation to classical macrophage activation by Mycobacterium bovis BCG exposure was monitored. Results indicate that this population can be activated both metabolically and functionally, as evidenced by enhanced release of superoxide anions and demonstrable tumoricidal activity against syngeneic and xenogeneic target cells. The pattern of metabolic activation of in situ tissue-associated macrophages differed somewhat from that of alveolar macrophages and was observed only after subsequent exposure of the cells to either zymosan particles or phorbol myristate acetate. Upon such exposure, the activated zymosan-treated tissue macrophages released approximately twice as much superoxide as the nonactivated cells and amounts comparable to the amounts released by activated alveolar macrophages. The tissue macrophages also displayed greater levels of cytotoxicity toward xenogenic targets than the alveolar cells and may have an important role in preventing microbial or tumor cell colonization of respiratory systems. PMID:2989181

  10. Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release.

    Science.gov (United States)

    Formica, S; Roach, T I; Blackwell, J M

    1994-05-01

    The murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic

  11. Sex-differential effect on infant mortality of oral polio vaccine administered with BCG at birth in Guinea-Bissau. A natural experiment.

    Directory of Open Access Journals (Sweden)

    Christine Stabell Benn

    Full Text Available BACKGROUND: The policy to provide oral polio vaccine (OPV at birth was introduced in low-income countries to increase coverage. The effect of OPV at birth on overall child mortality was never studied. During a trial of vitamin A supplementation (VAS at birth in Guinea-Bissau, OPV 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 was not part of the trial, but we noted whether the infants received OPV or not. OPV was missing during several periods in 2004. We used Cox proportional hazards models to compute mortality rate ratios (MRR of children who had received or not received OPV at birth. PRINCIPAL FINDINGS: A total of 962 (22.1% of the 4345 enrolled children did not receive OPV at birth; 179 children died within the first year of life. Missing OPV at birth was associated with a tendency for decreased mortality (adjusted MRR = 0.69 (95% CI = 0.46-1.03, the effect being similar among recipients of VAS and placebo. There was a highly significant interaction between OPV at birth and sex (p = 0.006. Not receiving OPV at birth was associated with a weak tendency for increased mortality in girls (1.14 (0.70-1.89 but significantly decreased mortality in boys (0.35 (0.18-0.71. CONCLUSIONS: In our study OPV at birth had a sex-differential effect on mortality. Poliovirus is almost eradicated and OPV at birth contributes little to herd immunity. A randomised study of the effect of OPV at birth on overall mortality in both sexes is warranted.

  12. Effects of BCG-polysaccharide nucleic acid on CD4+IL-17+ T cells and CD4+Foxp3+ Treg in asthmatic rats%卡介苗多糖核酸对哮喘大鼠CD4+IL-17+T细胞与CD4+Foxp3+调节性T细胞的影响

    Institute of Scientific and Technical Information of China (English)

    涂玲; 梁颖红; 魏明; 刘佳; 龚艳杰; 张俊华; 张宜花

    2015-01-01

    目的 观察卡介苗多糖核酸(BCG-PSN)对哮喘大鼠支气管肺泡灌洗液(BALF)、外周血和淋巴液中CD4+IL-17+T细胞(CD4+IL-17+T)与CD4+Foxp3+调节性T细胞(CD4+Foxp3+ Treg)百分比及IL-10、IL-17水平的影响及其可能机制.方法 SD大鼠60只随机分为对照组(n=15)、哮喘组(n=15)、BCG-PSN干预对照组(n=15)和BCG-PSN干预哮喘组(n=15).哮喘组和BCG-PSN干预哮喘组使用卵白蛋白建立大鼠哮喘模型,对照组和BCG-PSN干预对照组以等量生理盐水代替卵白蛋白,BCG-PSN干预哮喘组和BCG-PSN干预对照组均使用BCG-PSN进行干预.收集各组大鼠BALF、外周血和淋巴液,采用流式细胞术检测CD4+IL-17+T和CD4+Foxp3+ Treg百分比,酶联免疫吸附法(ELISA)检测IL-10和IL-17水平.结果 各组大鼠淋巴液中CD4+Foxp3+ Treg百分比、IL-10水平较BALF和外周血均明显升高(均P<0.01),CD4+IL-17+T百分比、IL-17水平较BALF和外周血均明显下降(均P<0.01).哮喘组大鼠BALF、淋巴液和外周血CD4+Foxp3+ Treg百分比、IL-10水平较其余3组均显著降低,而CD4+IL-17+T百分比、IL-17水平较其余3组均显著升高(均P<0.01).BCG-PSN干预哮喘组大鼠BALF、淋巴液和外周血CD4+Foxp3+ Treg百分比和IL-10水平较哮喘组显著升高(均P<0.01),与对照组和BCG-PSN干预对照组比较差异无统计学意义(均P>0.05).BCG-PSN干预哮喘组大鼠BALF、淋巴液和外周血CD4+IL-17+T细胞百分比、IL-17水平较哮喘组均显著下降(均P<0.01),与对照组和BCG-PSN干预对照组比较差异无统计学意义(P>0.05).结论 BCG-PSN可能通过调节哮喘大鼠外周血和淋巴液中CD4+Foxp3+ Treg和CD4+IL-17+T的百分比及相关细胞因子水平,改善机体免疫功能,从而减轻哮喘的炎性反应.%Objective To investigate the effect of BCG-polysaccharide nucleic acid (BCG-PSN) on the levels of CD4+IL-17+ T cells and CD4+Foxp3+ regulatory T cells(Treg),interleukin-10 (IL-10) and IL-17 in bronchoalveolar

  13. 液质联用技术分析比较基因重组卡介苗与传统卡介苗 Ag85复合体成分%Determination and comparing secretary antigen Ag85 complex components between gene recombinant BCG vaccine strain and traditional BCG vaccine strain by LC-MS

    Institute of Scientific and Technical Information of China (English)

    方习静; 刘蓉娜; 张海峰; 段凯; 闭兰

    2015-01-01

    目的:利用液质联用技术分析比较基因重组卡介苗Aeras-422与传统卡介苗的主要分泌型抗原Ag85复合体成分。方法分别提取基因重组卡介苗Aeras-422与传统卡介苗培养上清中的分泌蛋白,采用反相高效液相色谱(Reversed phase high performance liquid chromatography,RP-HPLC)进行分离,并将最终得到的目的蛋白峰采用基质辅助激光解吸电离飞行时间质谱仪( MALDI-TOF-MS ReflexⅢ)进行质谱分析鉴定。结果基因重组卡介苗Aeras-422与传统卡介苗培养上清分泌蛋白Ag85复合体成分有所不同,Aeras-422表达的Ag85复合体成分包括Ag85A和Ag85B两种抗原,传统卡介苗菌株仅分泌表达Ag85A抗原。结论基因重组卡介苗Aeras-422分泌Ag85复合体的能力优于传统卡介苗。为建立新型结核病疫苗的质控方法提供了数据支持。%Objective To establish a simple method for the determination and comparing the secretory antigen Ag85 protein complex components from two kinds of TB vaccine strains(AERAS-422 and Danish-SSI 1331 BCG vaccine).Methods Collecting the cultured supernatants of AERAS-422 and Danish-SSI 1331 BCG vaccine strains, the samples were concen-trated by ultrafiltration,then, analysed by reverse high performance liquid chromatography.Collecting the main peak to ana-lyse by SDS-PAGE, and the peaks of protein for mass spectrometric was determined using matrix assisted laser desorption/ionization time of flight mass spectrometry ( MALDI-TOF-MS ReflexⅢ) .Results By optimizing the reversed phase liquid chromatography separation process, the Ag85 mixture composition were further separated, and to establish Ag85A and Ag85B peak corresponding peptides mass spectrum maps by MALDI TOF-MS technology.The Ag85 complex has the differ-ent components in the cultured supernatants of two kinds of strain.Ag85 complex of Aeras-422 strain was composed with Ag85A and Ag85B.The traditional BCG vaccine strain only expressed

  14. 光动力疗法及其联合注射卡介苗对小鼠肝癌移植瘤的抑瘤作用与免疫反应%Tumor-suppressive Effect and Immune Reaction of Photodynamic Therapy Combined with Local Injection of BCG on Liver Carcinoma Xenografts in Mice

    Institute of Scientific and Technical Information of China (English)

    徐静; 张南征

    2011-01-01

    Objective To invest the local immune tumor-inhibition effect of photodynamic therapy (PDT) combined with local injection of BCG.Methods Ninety-six tumor-bearing models were established with liver carcinomas subcutaneously in mice. The mice were divided randomly into: control group, PDT group, BCG group, and PDT plus BCG group. Tumor size was measured in each group. The expression of F4/80 antibody was detected by immunohistochemistry in order to count the macrophages (MΦ) in the local tumor.Results ( 1 ) The tumor volume of PDT group, BCG group, and PDT plus BCG group was smaller than that of the control group 7 d after therapy (P <0. 01 ). The tumor volume of PDT plus BCG group was smaller than that of the PDT group 7 d after therapy ( P <0. 05 ). (2) 2 h, 24 h and 7d after therapy, immunohistochemical staining showed that the number of macrophages in the tumor of PDT group and PDT plus BCG group increased obviously (P <0.01 ) , compared with the control group and BCG group. The number of macrophages in the tumor of PDT plus BCG group increased obviously compared with the PDT group (P <0. 05).Conclusions PDT has the inhibitory effect on tumor growth of Heps cell line xenografts in mice, and can spontaneously induce the local immune effects. The therapeutic effect of PDT combined with BCG is superior to that PDT only.%目的 探讨光动力疗法(PDT)联合肿瘤局部注射卡介苗(BCG)的局部免疫反应及抑瘤效应.方法 建立小鼠Heps肝癌移植瘤模型96只,随机分为对照组、PDT组、BCG组和PDT+BCG联合组.观测各组移植瘤体积的变化.以F4/80抗体为标记,采用免疫组化法计数肿瘤局部巨噬细胞(Mφ)数量.结果 1.各治疗组治疗后7 d的移植瘤体积较对照组均明显缩小(P<0.01).联合组治疗后7 d的肿瘤体积较单纯PDT组明显缩小(P<0.05).2.免疫组化染色结果显示,PDT组和联合组治疗后2、24h和7 d肿瘤局部Mφ数量均明显高于对照组和BCG组(P<0.01).上述时间

  15. Two-step tuberculin skin testing in school-going adolescents with initial 0-4 millimeter responses in a high tuberculosis prevalence setting in South India.

    Directory of Open Access Journals (Sweden)

    Maitreyi Murthy

    Full Text Available BACKGROUND: The utility of two-step tuberculin skin testing among adolescents in high tuberculosis prevalence settings is not well established. OBJECTIVES: To determine the proportion and determinants of a 0-4 mm response to an initial standard tuberculin skin test (TST and evaluating 'boosting' with repeat testing. METHODS: Adolescents between 11 and 18 years attending schools/colleges underwent a TST; those with a response of between 0-4 mm had a repeat TST 1-4 weeks later. RESULTS: Initial TST was done for 6608/6643 participants; 1257 (19% developed a 0-4 mm response to the initial TST. Younger age and under-nutrition were more likely to be associated with a 0-4 mm response, while the presence of BCG (Bacillus Calmette Guerin scar and higher socio-economic class were less likely to be associated with a 0-4 mm response. On repeat testing boosting was seen in 13.2% (145/1098; ≥ 6 mm over the initial test while 4.3% showed boosting using a more conservative cutoff of a repeat TST ≥ 10 mm with an increment of at least 6 mm (47/1098. History of exposure to a tuberculosis (TB case was associated with enhanced response. CONCLUSION: The proportion of adolescents who demonstrated boosting on two-step TST testing in our study was relatively low. As a result repeat testing did not greatly alter the prevalence of TST positivity. However, the two-step TST helps identify individuals who can potentially boost their immune response to a second test, and thus, prevents them from being misclassified as those with newly acquired infection, or tuberculin converters. While two-step tuberculin skin testing may have a limited role in population- level TST surveys, it may be useful where serial tuberculin testing needs to be performed to distinguish those who show an enhanced response or boosters from those who indeed have a new infection, or converters.

  16. Expression of acid-sensing ion channels in rat articular cartilage with adjuvant arthritis%酸敏感离子通道在大鼠佐剂性关节炎关节软骨中的表达

    Institute of Scientific and Technical Information of China (English)

    袁凤来; 陈飞虎; 黄学应; 李霞; 吴繁荣; 阮晶晶; 李俊

    2008-01-01

    Objective To study the expression and significance of acid-sensing ion channels(ASICs)in rat articular cartilage with adjuvant arthritis. Methods Complete Freund's adjuvant(CFA) was prepared by suspending heat-killed Bacillus Calmette Guerin(BCG) in liquid paraffin at 10 mg/ml. CFA-induced arthritis was developed by injection of 100 μl CFA emulsion intradermally into the right hind paw. The morphological changes of articular tissues was observed by light microscope; RT-PCR and immunoblotting analyses were used to detect ASICs in rat articular cartilage with adjuvant arthritis. Results RT-PCR and western blot showed that ASIC1a, ASIC2a and ASIC3 were present in the articular cartilage of normal and model group, the ASICs mRNA levels in the model group were higher than in the normal group detected by semiquantitative analysis (P<0.01), ASICs protein levels in model group were higher than those in the normal group (P<0.01) when examined by immunoblotting. Conclusion The results show that the expression of ASICs in AA articular cartilage is enhanced and it may be related with articular cartilage breakdown.%目的 检测酸敏感离子通道(ASICs)在大鼠佐剂性关节炎关节软骨中的表达情况.方法 大鼠右侧后足跖皮内注射弗氏完全佐剂(CFA)诱导佐剂性关节炎(AA)大鼠模型,用半定量反转录-聚合酶链反应(RT-PCR)和Western blot方法检测ASICs在AA大鼠关节软骨的表达.结果 经半定量RT-PCR分析,ASIC1a、ASIC2a和ASIC3在AA大鼠关节软骨中的表达量明显高于正常组,差异有统计学意义(P<0.01);Western blot进一步检测显示蛋白表达的变化与mRNA变化一致.结论 AA大鼠关节软骨中ASICs的表达增多,可能与关节软骨破坏有关.

  17. The Use of Genomics in Microbiology: From Vaccines to Drug Resistance

    KAUST Repository

    Hill-Cawthorne, Grant A.

    2015-05-01

    Since 2004 sequencing has undergone a revolutionary change with the advent of first the 454 sequencer, followed by the introduction of the Solexa/Illumina chemistries. This has led to the ability to sequence the whole genomes of a large number of microorganisms in a short space of time. Microbiology’s last revolution was in the introduction of PCR, which allowed for faster detection of pathogens, particularly viruses. With whole genome sequencing (WGS) many of the time-consuming steps carried out by a reference laboratory can be skipped. These include organism detection, speciation, antimicrobial susceptibility testing, typing and molecular epidemiology – all carried out in a single sequencing run followed by bioinformatics analysis. So far the merits of WGS in microbiology have only been demonstrated in highly specialised scientific laboratories in high-income countries. However, with continuingly decreasing costs and increasing throughput, many public health laboratories are now acquiring sequencers and their use will inevitably spread to middle-income countries. In this thesis I explore the use of WGS in three specific areas and include details on how to develop and assess bioinformatics pipelines. First, I shall demonstrate that WGS can be used to assess highly divergent regions within microorganisms by using the example of the weaknesses in current approaches to the molecular detection of methicillin-resistant Staphylococcus aureus isolates. In particular, I shall highlight how current molecular tests have limitations in detecting drug resistance when the regions of the genome conferring resistance have significant mutations. Second, I will examine how WGS can provide insights into the biology of the current vaccine against tuberculosis, Bacillus Calmette Guerin (BCG), particularly how the continued passage of the seedlot for this vaccine has led to very different versions being used around the globe. Finally, I will demonstrate how WGS can be used to

  18. Analysis of Effect of Montelukast Sodium combined with BCG-PSN on Sick Children with Chronic Urticaria.%孟鲁司特联合卡介菌素治疗儿童慢性荨麻疹

    Institute of Scientific and Technical Information of China (English)

    吕广秀; 曹勇; 陈青青

    2012-01-01

      Objective The efficacy of the concept Chameng Lu Special Secretary and BCG polysaccharide nucleic acid injection treatment of chronic urticaria. Methods Control group with BCG Polysaccharide Nucleic Acid Injection 0.5mg every other day, intramuscular injection, 10d1 courses, a total of three courses, the experimental group add services on the basis of montelukast oral daily 5mg, per nightorally once. Results Results of 117 cases ,the 59 was for test group , and 58 for control group .The effective rate of test group was 88.1%, while 70.7% for control group ,the difference had statistically significant (P<0.05).Conclusion BCG-PSN was effective for treatment chronic urticaria in children ,and BCG-PSN combined with Montelukast could raise the treating effect of sick children with chronic urticaria ,and reduce the recurrence .%  目的观察孟鲁司特和卡介菌多糖核酸注射液治疗慢性荨麻疹的疗效.方法对照组单用卡介菌多糖核酸注射液0.5mg,隔日一次,肌内注射,10d1个疗程,共计3个疗程,实验组在此基础上加服孟鲁司特口服,每天5mg,每晚一次口服.结果共治疗117例,实验组59例,对照组58例,实验组有效率为88.1%,对照组有效率为70.7%,两组比较差异有统计学意义(P <0.05).结论孟鲁司特联合卡介菌素多糖核酸注射液治疗可提高儿童慢性荨麻疹病的疗效,以减少复发率.

  19. 2009-2011年度汕头市新生儿卡介苗接种质量调查%Survey on BCG Vaccination Quality in Shantou City from 2009 to 2011

    Institute of Scientific and Technical Information of China (English)

    李晓云

    2013-01-01

      目的评价汕头市2009—2011年新生儿卡介苗接种效果,并探索卡痕与结核菌素反应之间的关系.方法观察10477例接种卡介苗后满12周婴儿卡痕形成情况,并对其进行结核菌素皮试,分析皮试结果.结果在10477例婴儿中,结核菌素试验阳性率93.13%,卡痕率94.83%;卡痕合格者,结核菌素反应阳性率和反应直径大于卡痕不合格者(P<0.05).结论汕头市新生儿卡介苗接种效果良好,卡痕合格者结核菌素试验阳性率高,但卡痕反应并不证明产生免疫力的高低,而用结核菌素试验评价结核免疫水平是目前唯一可靠、准确的方法.因此,应推广结核菌素试验并提高卡介苗接种质量.%Objective To evaluate the BCG vaccination quality of new born babies in Shantou from 2009 to 2011, and discuss the relationship between BCG scar and tuberculin reaction. Methods A total of 10 477 babies’ scars 12 weeks after vaccination were observed, and the positive rate was analyzed by PPD test. Results Of the total, positive rate of PPD test reached 93.13%. And 9 935 babies had scars with the scar rate of 94.83%. The positive rate of PPD and reacted diameter of new born babies with scar size greater than or equal to 3 mm were obviously higher and bigger than those with scar size less than 3 mm. The difference was statistical significance (P<0.05). Conclusion The quality of new born babies’ BCG vaccination in Shantou maintains good. There is positive correlation between the scar size and the PPD test positive rate. The scar is only the evidence of vaccination, which cannot indicate the immunity level and PPD test is the only reliable and correct approach to measure the tuberculosis immunity level up to now. To guarantee the vaccination quality, technique of BCG vaccination needs to be bolstered.

  20. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    Science.gov (United States)

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

  1. Análise da positivação do teste tuberculínico, após administração da vacina BCG, pela via oral, a crianças sadias

    Directory of Open Access Journals (Sweden)

    Yvone Khairallah de Oliveira e Silva

    1974-10-01

    Full Text Available Efetuaram os autores teste tuberculínico, com PPD (RT 23, 10 UT, em 3.6S4 crianças sadias, que receberam, pela via oral, em três oportunidades separadas por intervalos de um mês, vacina BCG líquida ou liofilizada e placebo representado por preparação sem bacilos. Dois grupos foram basicamente estabelecidos, tendo os limites etários correspondido a noventa dias em um deles e a essa idade e quinze anos no outro. Considerando os módulos com tamanhos superiores a cinco milímetros, observaram taxas de positividades de 37,6% e 21% relativamente aos indviduos separados da maneira citada e em avaliações levadas a efeito no máximo nove meses depois, mas as cifras pertinentes ao produto isento de bacilos álcool-ácido-resistentes e ao submetido à liofilização mostraram-se expressivamente menores. Valorizada somente a alergização, as percentagens indicadas e não desprezíveis atestaram a ocorrência de destacada absorção, sobretudo ao ser levado em conta o sucedido quanto às pessoas de menores idades.Oral BCG vaccine, either liquid or liophyllized, or a placebo was administered in three monthly doses to 3,684 healthy children. The study population was divided in two great groups, one to ninety days of age and the other from nine y days to jifteen years of age. A tuberculin test, with PPD (RT 23, 10 TU, was performed up to nine months later on each child, corsidering a nodule layer than five millimeters as a positive test. A positive incidence of 37.6% and 21% was found for the younger and the older age groups, respectively, who reccived liquid BCG. The children who took liophyllized BCG or placebo showed significantly smaller incidences. If allerginization moy be valued, then it can be seen that there is significant absortion, especially in the younger subjects

  2. Estudo sobre a evolução do risco de infecção tuberculosa em área com elevada cobertura por BCG The trend in the risk of tuberculous infection in an area with wide coverage with BCG vaccination

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1985-04-01

    Full Text Available A partir da prevalência de infecção tuberculosa em escolares com 7 anos de idade, calculou-se a taxa de redução do risco anual de infecção na cidade de São Paulo (Brasil, entre 1974 e 1982. Nesse período o declínio médio foi de 5% ao ano. Nas 59 escolas municipais pesquisadas não houve correlação entre a cobertura de vacinação BCG e a prevalência de infecção natural em não-vacinados, à idade estudada. A alergia tuberculínica no grupo de crianças vacinadas, que recebeu a vacina em alguma idade anterior entre o 1° e o 6° ano de vida, revelou-se 2,5 vezes mais intensa do que a alergia no grupo de mesma idade (7 anos, não vacinado previamente. Foram feitos comentários quanto à impropriedade do material utilizado com vistas ao cálculo do verdadeiro valor do risco de infecção tuberculosa na área em questão.The estimation of the risk of tuberculous infection from prevalence data obtained at school-age, in 1974 and in 1982, permitted the determination of the relevant trend in the city of S. Paulo, Brazil, between those years. The risk of infection decreased, on average, by 5% annually during the period. There was no evidence of any association between the proportions of vaccinated children and that of infected children among those unvaccinated, in the 59 schools studied. Tuberculin sensitivity in 7 years old school-children, vaccinated with BCG at any age between the 1st and the 6th year of life was 2.5 times more intense than that in unvaccinaetd children of the same age. With regard to the calculation of the true value of the risk of tuberculous infection, commentaries about the unrealiability of the available data were made.

  3. 多房棘球绦虫重组BCG-EmⅡ/3疫苗诱导小鼠脾细胞因子变化的研究%Study on the changes of cytokines of splenocytes in mice by immunization with recombinant BCG-Em Ⅱ/3 vaccine against Echinococcus multilocularis

    Institute of Scientific and Technical Information of China (English)

    李文桂; 王鸿; 朱佑明

    2008-01-01

    Objective To investigate the changes of cytokines of splenocytes in mice immunized with recombinant BCG-Em Ⅱ/3 vaccine of Echinococcus multilocularis(Em)and consequently challenged with Em protoscoleces.Methods Balb/c mice were subcutaneously or intranasally vaccinated and challenged with Em were separated and cultured with EmAg,ConA or PHA,respectively.The supematants were gathered to measure the levels of IL-2,IFN-γ,TNF-α.and IL-4 by ELISA Kits.Results The levels of IL-2,IFN-γ,TNF-α and IL-4 in the subcutaneous group were(34.6±2.7),(34.5±2.8),(265.0 ±0.0)and(9.8±2.6)ng/L respeetively:those in the intranasal group were(32.5±2.2),(33.6±2.7),(130.0±0.0)and(10.4±27)ng/L respectively;those in the control were(25.0±1.9),(30.0±0.0),(10.0±0.0)and(12.5±2.7)ng/L,respectively:there were statistical differences between the immunized groups and control group(P<0.01 or<0.05);The level of TNF-α in the subcutaneous group was higher than that in the intranasal group.Conclusion Th1 response has been induced in mice vaccinated with rBCG-Em Ⅱ/3 vaccine and challenged with Em protoscoleces.%目的 探讨多房棘球绦虫(Em)重组BCG-EmⅡ/3疫苗免疫和Em原头节攻击后小鼠脾细胞因子的变化.方法 将Balb/c小鼠按体质量随机分为3组:疫苗皮下注射组、疫苗鼻腔内接种组、对照组.免疫后8周用Em原头节进行攻击感染,感染后18周杀鼠取脾,分离脾细胞,分别用原液、Em抗原(EmAg)、刀豆蛋白A(ConA)或植物血凝素(PHA)培养,酶联免疫吸附(ELISA)法检测脾细胞培养上清液中白细胞介素2(IL-2)、γ干扰素(IFN-γ)、肿瘤坏死因子α(TNF-β)、白细胞介素4(IL-4)水平.结果 疫苗皮下注射组原液培养条件下IL-2、IFN-γ、TNF-α和IL-4水平分别为(34.6±2.7)、(34.5±2.8)、(265.0±0.0)、(9.8±2.6)ng/L,与对照组[(25.0±1.9)、(30.0±0.0)、(10.0±0.0)、(12.5±2.7)ng/L]比较差异均有统计学意义(P<0.01或<0.05);疫苗鼻腔内接种

  4. 运用护理干预配合药物治疗卡介苗混合伤寒疫苗误种效果分析%Use of drugs and nursing intervention for the treatment of BCG vaccine BCG mix typhoid vaccine according to the analysis of the effect

    Institute of Scientific and Technical Information of China (English)

    李白; 陆克; 李惠兰; 黄丽芹

    2016-01-01

    目的:评价运用护理干预辅以药物治疗处理卡介苗混合伤寒疫苗误种皮下效果分析 ,以期为预防接种事故处理提供参考.方法:及时告知家长疫苗误种不良反应和处理措施 ,消除家长恐惧心理 ,对儿童及时局部封闭和药物治疗.结论:及时处理避免发生脓肿或溃疡 ,护理干预可以显著降低不良反应发生 ,化解家长与医务人员对立情绪 ,消除预防接种工作不良影响具有明显的社会效益 ,值得推广运用.%Objective :to evaluate the BCG vaccine mixed by nursing intervention with drug treatment of typhoid vaccine by subcutaneous effect anal-ysis ,so as to provide reference for vaccination incident handling .Methods :inform parents mistakenly adverse reactions and treatment measures ,elimi-nate parents fear ,timely local closed and drug treatment for children .Conclusion:nursing intervention can significantly reduce adverse reaction ,dis-solve the parents and the medical staff antagonism ,eliminate the vaccination work effects has the obvious social benefits .

  5. A Novel Synthetic Mycolic Acid Inhibits Bronchial Hyperresponsiveness and Allergic Inflammation in a Mouse Model of Asthma

    OpenAIRE

    KIM, YOUNG-JOON; Kim, Ha-Jung; Jeong, Se Kyoo; Lee, Seung-Hwa; Kang, Mi-Jin; Yu, Ho-Sung; Jung, Young-Ho; Seo, Ju-Hee; Kim, Byoung-Ju; Yu, Jinho; Park, Seoung-Ju; Lee, Yong-Chul; Hong, Soo-Jong

    2013-01-01

    Purpose Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma. Methods BALB/c mice were injected intraperitoneally with sMA follow...

  6. Mucosal SIV vaccines comprising inactivated virus particles and bacterial adjuvants induce CD8+T-regulatory cells that suppress SIV positive CD4+cell activation and prevent SIV infection in the macaque model.

    OpenAIRE

    Jean Marie eAndrieu; song echen; Chunhui eLAI; weizhong eguo; Wei eLu

    2014-01-01

    A new paradigm of mucosal vaccination against HIV infection has been investigated in the macaque model. A vaccine consisting of inactivated SIVmac239 particles together with a living bacterial adjuvant (either the Calmette & Guerin bacillus, lactobacillus plantarum or Lactobacillus rhamnosus) was administered to macaques via the vaginal or oral/intragastic route. In contrast to all established human and veterinary vaccines, these three vaccine regimens did not elicit SIV-specific antibodies n...

  7. C02 Laser Plus BCG-PSN Injection in Treatment of Genital Condyloma Acuminata%C02激光联合卡介菌多糖核酸针治疗生殖器尖锐湿疣疗效观察

    Institute of Scientific and Technical Information of China (English)

    朱亚丽

    2011-01-01

    目的 观察C02激光联合卡介苗素(医学名为卡介菌多糖核酸针,BCG-PSN)治疗生殖器的尖锐湿疣.(CA)的疗效.方法 将126例CA患者随机分为两组,治疗组用C02激光联合BCG-PSN进行治疗,具体措施:用CO:激光割开尖锐湿疣体,然后向其里面注射BCG-PSN注射液2mL,每隔一日进行再肌注,总共9次为1个疗程;对照组只在局部麻醉药物作用下用CO:激光治疗.结果 联合治疗组1次治愈率达到了89.23%,对照组仅为57.38%,两组间有明显的差异(P<0.05).结论 CO,激光联合BCG-PSN治疗尖锐湿疣明显优于单独运用C02激光治疗的方法.

  8. HIV阳性母亲所娩儿童国家免疫规划5种疫苗接种现状调查%Survey On vaccination status of five vaccines belongs to NIP among the children with HIV positive mother

    Institute of Scientific and Technical Information of China (English)

    黄宝卫

    2011-01-01

    目的 了解HIV阳性母亲所娩儿童国家免疫规划(National Immunization Program,NIP)5种疫苗[卡介苗(Bacillus Calmette Guerin,BCG)、口服脊髓灰质炎减毒活疫苗(Oral Poliomyelitis Attenuated Live Vaccine,OPV)、百日咳-白喉-破伤风联合疫苗(Diphtheria-Pertussis-Tetanus Combined Vaccine,DPT)、麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)、乙型肝炎疫苗(Hepatitis B Vaccine,HepB)]的接种现状,探讨提高预防接种率的方法.方法 随机抽查鹿寨县2005-2008年HIV阳性的部分产妇,对这些产妇所娩的48名儿童的预防接种资料进行分析.结果 HIV阳性母亲所娩儿童的OPV、DPT、MV、HepB接种情况较好.BCG接种率和HepB及时率相对较低;OPV、DPT、MV、HepB的单苗合格接种率95%以上,BCG单苗合格接种率和5苗全程合格率分别为85.42%、83.33%.结论 儿童"五苗"接种较好,接种人员严格掌握接种禁忌及提高受种者监护人的预防接种意识,有利于提高NIP疫苗接种率.%Objective To understand the vaccination status of five vaccines belong to national immunization program among children whose mothers were HIV positive, five vaccines were Calmette Cuerin Vaccine ( BCG) . Oral Poliomyelitis Attenuated Live Vaccine (OPV) . Diphtheria - Pertussis - Tetanus Combined Vaccine ( DPT) , Measles Attenuated Live Vaccine ( MV) . Hepatitis B Vaccine ( HepB) . Study the method for improving the immunization rate. Method Randomly sampled and analyzed the vaccination information of 48 children whose mothers were HIV positive during 2005 to 2008 of Luzhai County. Results The vaccination situation of OPV、 DPT、 MV、 HepB among the children were better, BCG vaccination rate and HepB timeliness rate were relatively low. Single qualified vaccination rate of OPV、 DPT、 MV、 HepB were more than 95% . BCG qualified vaccination rate and whole - course qualified vaccination rate of five vaccines were 85. 42% 、83. 33%. Conclusions Coverage rates

  9. Research and Application of Industrial BCG Matrix ——Sampled from Shenzhen%产业发展战略的波士顿矩阵导人分析与修正——以深圳为例的实证研究

    Institute of Scientific and Technical Information of China (English)

    代明; 韩启钰

    2011-01-01

    Industrial BCG Matrix is an industry analysis model evolving from BCG Matrix applied in in- dustry analysis. Industrial BCG Matrix is based on Industrial Life Cycle theory, divided into four industry types with Horizontal ordinate of industrial development gradient and y - axis of industrial development quality, coin- ciding in four stage of industry life cycle. To analysis industrial development foundation and industrial develop- ment potential, we form an industrial development gradient and industrial development quality system of evalu- ation, and select industrial development strategy by CARDS model. Finally, this paper examines the practical- ities, advantages and disadvantages of Industrial BCG Matrix with an example sample of Shenzhen with a conclusion of some disadvantages and suggestion for improvement of application of Industrial BCG Matrix.%产业型波士顿矩阵以产业生命周期为理论基础,产业发展梯度及产业发展质量为横纵坐标,融合两维时间概念,划分出四类基本产业类型,吻合产业生命周期的四个阶段。论文构建了产业发展质量和发展梯度的评价指标体系来分析产业发展潜力与发展基础,并结合CARDS模型来分析产业发展战略的选择。最后,以深圳为例来检验产业型波士顿矩阵的实用性和优缺点,并提出它在实际应用中存在的一些缺陷及改进建议。

  10. The Study On Construction, Immunogenicity and Protection Against Mycobacterium tuberculosis of mpt64-recombinant BCG Vaccine%mpt64-卡介苗重组疫苗的构建、免疫原性及抗结核作用

    Institute of Scientific and Technical Information of China (English)

    孙颖; 张灵霞; 吴雪琼; 董恩军

    2011-01-01

    It was aimed to construct mpt64-recombinant BCG vaccine to find an improved vaccine to replace BCG and to prevent TB effectively. The gene of MPT64 was amplified by PCR and recombined with shuttle plasmids pYUB295. The recombinant shuttle plasmid was identified by PCR, enzyme digestion and DNA sequencing and then transformed into BCG by electroporation. The antigen-specific antibody levels of mouse immunized with recombinant BCG were evaluated by ELISA and multiplication of mouse lymph-cell was detected by MTS. The protection against M. tuberculosis of recombinant BCG vaccines was tested by their prevention and treatment experiments. PCR, enzyme digestion, DNA sequencing and SDS-PAGE results showed: The mpt64-recombinant BCG was constructed successfully and can express extrinsic MPT64 gene. The immunity experiment showed :extrinsic gene can be expressed in BCG and can stimulate B cell to produce antibody,the antibody level reached the peak after 45 days; The lymph-cells of each group proliferated when stimulated by different antigen,all stimulation index reached 2. The stimulation index of each group had no obviously difference. The prevention experiment of recombinant BCG against M. tuberculosis was indicated: mpt64-recombinant BCG and BCG can extend mean time to death and reduce death rate in 2 month of those mouse, the protection effect of mpt64-recombinant BCG had no difference with BCG. It could be concluded that the mpt64-ecombinant BCG was constructed successfully. The protection effect of mpt64-recombinant BCG had no difference with BCG.%通过基因工程重组技术将结核分枝杆菌保护性抗原MPT64的编码基因与穿梭质粒载体pYUB295重组,采用电穿孔技术将重组质粒导入到卡介苗中,应用聚合酶链反应(PCR)扩增、聚丙烯酰胺凝胶电泳(PAGE)对mpt64-卡介苗重组疫苗鉴定:成功地构建了MPT64基因pYUB295重组质粒,MPT64蛋白在卡介苗中能分泌表达.卡介苗重组疫苗免